Friday, October 26, 2012

Arsenic in Rice: Part 17 - The Ethical Considerations of a Threshold

Consumer Reports writes:
Consumers Union, the advocacy arm of Consumer Reports, urged the FDA to set a 3 ppb limit for total arsenic in apple and grape juice.
They are advocating for that level, which would then also be used for rice:
Using the 5-ppb [New Jersey] standard in our study, we found that a single serving of some rices could give an average adult almost one and a half times the inorganic arsenic he or she would get from a whole day’s consumption of water, about 1 liter. (CR)
Consumer Reports is advocating for a line to be drawn.  On one side the product will be "safe" - or - not  "troubling," "worrisome," "cause for concern," or "potentially harmful."  The question that needs to be asked is what will rice and apple juice that falls on the other side - more than 3 ppb - be called?



That's a question that seems to get brushed aside or, most likely, not even considered.  And here is where the ethical considerations of a threshold must be taken into consideration.

The reason that New Jersey decided that 5 ppb was "safe" for their water was because they could not effectively treat the water to anything below that.  Remember, their law demands a one in one million risk which means that the water would need to be treated to 0.003 ppb.  Not only is that not possible to treat down to, it is also not possible to analyze with any degree of precision and accuracy.

So New Jersey settled on 5 ppb as being reasonably able to attain:
This determination comports with the NJSDWA mandate to establish the MCL at the most protective level within the constraints of medical, scientific and technological feasibility. (NJ)
But that threshold is for water.  We can "waste" water if it cannot be treated, use it for non-consumption purposes.  That treatment option is not available for apple juice and rice that exceeds the threshold of 3 ppb.  So what would happen to it?  Would it need to be destroyed?  And if so, would the "wasting" of that apple juice, or more specifically rice, that contains 4 ppb inorganic arsenic be ethical?

First, let's settle on what I mean by "ethical":
Ethics refers to well-founded standards of right and wrong that prescribe what humans ought to do, usually in terms of rights, obligations, benefits to society, fairness, or specific virtues. (1)
The ethical consideration rears its ugly head when you draw that line in the sand.  If Consumer Reports wants a 3 ppb standard, what will be done with rice and apple juice that is found to contain 4 ppb?

If 3 ppb is "safe" then exceeding that number - appearing on the other side of that line is...what?
  • We are not talking about water here.  We are talking about a food.  You cannot treat rice or apple juice that is found to contain 4 ppb of inorganic arsenic, so what do you do with it?
  • Well we could blend it to dilute the total to below the 3 ppb - you know, the solution to pollution is dilution approach.  But that assumes that we have the capacity to store and blend this volume.
  • We could just dispose of it, but that means that we take that rice out of the food supply thereby denying rice to citizens that can no longer afford it.  Economics 101 in play: supply and demand sets the price,
  • We stop growing rice and apples in areas where the arsenic shows up in the samples.  Sounds good.  But you can't just plant an apple tree and start producing apples - it takes a long time to grow..  Nor can you grow rice anywhere - it take access to a lot of water.  Besides, look at the numbers for both apple juice and rice.  Arsenic is EVERYWHERE and in EVERY sample. It is ubiquitous with these two products because it is an element and it is in the water and soil cycle (see my previous post).
Well, that leaves us then with this.
  • We could give it to poor people or starving people.  That's a better alternative for them.  If you are hungry, what difference does it make?  And in areas where food is short, those folks will die from starvation long before bladder cancer ever manifests itself.
If you draw a line in the sand at some ppb, you either dilute it, waste it, or give it to others when that threshold is exceeded.

You see the problem now with a line in the sand?  That line had better be bullet-proof or the ethical considerations that will come into play will rear their ugly head.  If you say 3 ppb is "safe" then wasting rice and apple juice when it contains 4 ppb will raise the cost of these two items and take them out of being consumed.  We can live without apple juice, but rice?

If you say that 4 ppb is not bad enough to waste, then where do you draw the line as to when it must be wasted?  And who gets to consume the 4 ppb product?  Do wealthy people get to eat the 3 ppb and less while the poor and hungry get the above threshold product?  Would that be fair?

Is that ethical?  Is that what we ought to do?

What will the rice and apple juice that exceeds the "3 ppb limit" be classified as?  Consumer Reports calls rice above 5 ppb "troubling," "worrisome," "cause for concern," or "potentially harmful."  If they push for a 3 ppb limit, as they are advocating for apple juice, then how can they justify a 5 ppb limit for rice?  Rice will therefore have to also meet the 3 ppb limit per serving to be "safe."

Here is what I want Consumer Reports to respond to:
  1. What will rice and apple juice be considered if it exceeds the 3 ppb limit they urge the FDA to set?
  2. What must be done to rice and apple juice that exceeds this threshold of 3 ppb?
  3. Can rice and apple juice that exceeds 3 ppb be given to starving people and/or the poor, and, if so, how is that ethical?
And my final question:
  • If exceeding the threshold is considered "potentially harmful" or to increase risk, how can we ethically allow anyone to consume this rice and apple juice?
The answer is you can't. Once you draw a line in the sand, anything that appears on the other side must be the opposite of what you want.  Safe: Unsafe, Healthy: Unhealthy, Toxic: Non-Toxic,  Okay: Not Okay, Good: Bad.

It is one or the other, it cannot be both.

So I'll end with this:

If you are going to draw a line in the sand, that line better represent a real risk if you step over it.  Does stepping over a 3 ppb limit represent a real risk?  Does eating a 1/4 cup serving of rice with 9.6 ppb inorganic arsenic represent a real risk?  If it does, then it is "potentially harmful."  If it does not, then it is safe.

It cannot be both.  This is why we must choose a threshold that represents a real potential for harm.  When you do, those ethical considerations become much more manageable when you exceed the threshold. We have an obligation to protect public health.  We have an obligation to feed people.  We have an obligation to look at the data and make sound decisions when setting a threshold of what is, and is not "safe."


Part 17 - Creating a Needless Concern.

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Monday, October 22, 2012

Arsenic in Rice: Part 16 - Rice Eaters and Bladder Cancer

Consumer Reports tells their readers:
Our resulting analysis of 3,633 study participants found that on average, people who reported eating one rice food item had total urinary arsenic levels 44 percent greater than those who had not, and people who reported consuming two or more rice products had levels 70 percent higher than those who had no rice.
This leads them to view the arsenic they detected in food products as such:
“Despite our taking into account other common sources of arsenic, and no matter which way we sliced the data, we see a very strong association between rice consumption and arsenic exposure,” says Stahlhut, who along with Navas-Acien led a similar analysis of NHANES data for our January 2012 article on arsenic in juice. That analysis found that study participants who reported drinking apple or grape juice had total urinary arsenic levels that were on average nearly 20 percent higher than those who didn't.
 Which leads them to this conclusion:
Consumers Union, the advocacy arm of Consumer Reports, urged the FDA to set a 3 ppb limit for total arsenic in apple and grape juice.
I am going to come back to that...but right now we still need to look at what we know so far.
  • Urinary arsenic concentrations give a good biomarker of the absorbed dose of arsenic, since about 70% is excreted in the urine. (AJE)
  • Rice eaters had arsenic levels that were 44 percent greater than those that do not consume rice. (CR)
  • The average amount of rice consumed is one cup. (EHP)
  • Consumer reports measured the amount of inorganic arsenic in one serving of rice and found the highest level to be 9.6 μg per 1/4 cup. (CR)
In my last post I attempted to show what is in play:
  • ...if a 1/4 cup serving size that exceeds the New Jersey drinking water standard of 5 ppb is considered by Consumer Reports to be "troubling," "worrisome," "cause for concern," or "potentially harmful." 
  • ....consuming one full cup of this rice must therefore result in four times more "troubling," "worrisome," "cause for concern," or "potentially harmful."
In all my previous posts I have tried to show that "troubling," "worrisome," "cause for concern," or "potentially harmful," that results from consuming 1/4 cup of rice that exceeds the New Jersey drinking water standard of 5 ppb for arsenic must be because of some risk of harm.

Because Consumer Reports sees harm if a serving is above 5 ppb, that harm must therefore be based on bladder cancer since that is what the NRC based the slope factor on used to support New Jersey's 5 ppb drinking water standard.

And because bladder cancer is also what IRIS is using for the Cancer Slope Factor - potency - they propose for arsenic, exceeding any number above "0" for arsenic increase the risk of bladder cancer.  New Jersey accepts a one in one million risk as acceptable which means 0.003 μg/L would be considered "safe."  Understanding reality, NJ set on a limit of 5 μg/L as acceptable based on the ability to treat the water as well as accurately test for an amount that low.  Therefore 0.003 μg/L "safe" became "safe" at 5 μg/L.

I then looked at urinary total arsenic that was reported by the CDC.  This led me to write in my last post:
So...if Mexican Americans and Asians consume more rice than Whites...and rice eaters have more urinary total arsenic than non-rice eaters...and the Cancer Slope Factor assume a potency whereby consuming more increase the risk harm...and that potency was used to that justify the New Jersey drinking water level of 5 ppb...and that Cancer Slope Factor, now proposed by the IRIS, is based on bladder cancer in woman...
Which I concluded with this:
...we would, therefore, expect to see more bladder cancer in Mexican Americans and Asians, especially in women...shouldn't we?
I want to stress here that all of my sources are the same sources as used by Consumer Reports and their experts.  They are all from reputable sources.  I am looking at the same data, facts, and figures that they look at and I don not see "troubling," "worrisome," "cause for concern," or "potentially harmful," for any of the rice they tested.

We are missing a lot, and I do mean a lot, of data to conclude "troubling," "worrisome," "cause for concern," or "potentially harmful," when exceeding 5 ppb per serving up to a maximum of 10 ppb.

If rice eaters have more urinary total arsenic then non-rice eaters, should we see more bladder cancer in those groups that consume rice on a daily basis?  So back to this question I posed:
...we would, therefore, expect to see more bladder cancer in Mexican Americans and Asians, especially in women...shouldn't we?
I went to the National Cancer Institute and looked up the data on bladder cancer from the Surveillance and Epidemiology and End Result (SEER) database.  Here is what they say:

Source

Now, with those estimate numbers in mind, let's look at what the EPA's IRIS is basing the proposed arsenic Cancer Slope Factor on:

2010 Draft IRIS Page 150-151


The EPA is proposing a Cancer Slope Factor on women's risk for bladder cancer.  This means that women appear to be more susceptible to the harm of bladder cancer from exposure to arsenic.  The "potency" of arsenic as a bladder cancer carcinogen is based on women and bladder cancer.  All things considered, when consuming a cup of rice, women and men receive the same dose of arsenic.  Same with drinking water.  There is a slight difference in urinary total arsenic between men and women.

CDC

If women are more susceptible to bladder cancer - the life-time risk - then wouldn't we see a higher incidence in women since consumption of arsenic seems to be the same?  That Cancer Slope Factor is derived from a line drawn through data points that looked at arsenic dose and incidence of cancer.  It assumes that there is a linear relationship between what was seen at high doses (the Morales data) and what should - theoretically - be seen at low doses.  It assumes a line going all the way to zero.  Zero dose, Zero risk of bladder cancer.

Let's look at those numbers in terms of an incidence rate for bladder cancer:

Source
EPA's proposed IRIS Cancer Slope Factor assumes a "safe" concentration of arsenic for a risk of one in 10,000 to be 0.14 μg/L (which is based on a consumption of 2 liters of drinking water per day).

Let's look at the incidence of bladder cancer in rice eaters.  Notice how Asians and Hispanics, two groups we know consume rice, have lower bladder cancer incidence than whites for both men and women.

I don't know...the numbers just don't support the theoretical potency for arsenic and bladder cancer the EPA is proposing.  Dr. Honneycutt with the TCEQ elaborates the same observation:
For bladder cancer alone, the incidence risk calculated by USEPA based on final draft values for males/females is 3.1E-04 per μg/L. Therefore, based on 2 μg/L as an average drinking water concentration, the estimated bladder cancer risk for the US population would be 6.2 per 10,000 or 62 per 100,000. However, the actual occurrence of bladder cancer in the US is about 23 cases per 100,000 (males/females combined). It would take 3 times the actual bladder cancer incidence for US males/females combined to even make possible the 62 cases per 100,000 estimated due to arsenic exposure from drinking water alone. Thus, the incidence risk calculated by USEPA final draft values for bladder cancer appears to be inaccurate and overly conservative. (emphasis mine)
Which brings us to this point.

If the theoretical Cancer Slope Factor is based on bladder cancer, and the incidence of bladder cancer does not match the theoretical risk being calculated, should we accept the theoretical risk as the basis for determining a "safe" threshold or for "establishing health criteria?"

If that Cancer Slope Factor proposed by EPA does not estimate the bladder cancer risk correctly, exceeding the New Jersey 5 ppb threshold for a 1/4 serving of rice will not be "troubling," "worrisome," "cause for concern," or "potentially harmful."

And if that's true, advocating for a "3 ppb limit for total arsenic in apple and grape juice" - which would be carried over for rice - is not warranted.

That's an important point to acknowledge.  It is the whole reason I spend time writing these posts.  If we are going to draw a line in the sand and claim "safe" on one side, then we will need to address what will it mean for the products that have concentrations above that threshold and fall on the other side of the line?



Not only does the science behind toxicology demand that we get this right, there are ethical considerations that need to be made as well.


Next Post: Arsenic in Rice: Part 17 - The Ethical Considerations of a Threshold


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Sunday, October 21, 2012

Arsenic in Rice: Part 15 - Urine From Rice Eaters

Continuing on...

Here is what we have been told so far:
  • Urinary arsenic concentrations give a good biomarker of the absorbed dose of arsenic, since about 70% is excreted in the urine. (AJE)
  • Rice eaters had arsenic levels that were 44 percent greater than those that do not consume rice. (CR)
  • The average amount of rice consumed is one cup. (EHP)
  • Consumer reports measured the amount of inorganic arsenic in one serving of rice and found the highest level to be 9.6 μg per 1/4 cup. (CR)
For those of you who are interested in how consumer Reports came up with that value of 9.6 μg per 1/4 cup, I am going to assume it was based on this methodology.  Consumer Reports "PDF with complete details of our test results" lists the concentration of inorganic arsenic as a part per billion (ppb).

PDF with complete details of our test results
214 ppb is most likely from a weight to weight analysis.  So in this case there were found to be 214 μg of inorganic arsenic per kilogram (kg) of rice.  Consumer Reports calculates a 1/4 cup serving size to contain 45 grams of rice:


Using some algebra...if one kg of rice contains 214 μg of inorganic arsenic, 45 grams of rice will contain 9.63 μg, and that concurs with what Consumer Reports shows in their report:


So the next question will be, what amount of inorganic arsenic do folks actually consume?  This is where it gets a bit tricky.  It seems that the results on urinary arsenic is for total arsenic.  We want to look at inorganic arsenic, the form of arsenic that may contribute to bladder cancer.

With that in mind, let's assume that the total urinary arsenic is inorganic arsenic.  Here is what we find, according to the Centers for Disease Control (CDC)

CDC
Consumer Reports tells us that "people who ate rice had arsenic levels that were 44 percent greater than those who had not," and "certain ethnic groups were more highly affected, including Mexicans, other Hispanics, and a broad category that includes Asians."

You can see that Mexican Americans have a higher mean urinary total arsenic than non-Hispanic whites, but non-Hispanic blacks are even higher.  What we don't have is data on Asians.  Now, based on all of this, rice eaters consume more arsenic than non-rice eaters.  This is confirmed by the Dartmouth study on children:
Results: The median total urinary arsenic concentration among children who reported consuming rice was 8.9 μg/L  compared with 5.5 μg/L among those who did not consume rice. 
That median is based on 1/4 cup of rice.  The Dartmouth researches also report:
After adjusting for potentially confounding factors, and restricting the study to participants who did not consume seafood in the preceding 24 hr, total urinary arsenic concentration increased 14.2% with each 0.25 cup increase in cooked rice consumption.
What we know now is that rice consumption is a potential source of arsenic exposure.

Assuming that the impact for rice and water on the total urinary arsenic is similar for an adult as it is for a child...and considering that the mean reported by the CDC is for both rice eaters and non-rice eaters, we can assume that a Mexican American eating one cup of rice would have approximately 15.8 μg/L urinary total arsenic. (9.29 x 1.142 = 10.6 X 1.142 = 12.1 x 1.142 = 13.8 x 1.142 = 15.8)

Dr. Smith tells us - based on the Mormon cohort research he cited:
Urinary arsenic concentrations give a good biomarker of the absorbed dose of arsenic, since about 70% is excreted in the urine.  Excretion of arsenic in urine as a function of exposure to arsenic in drinking water. (AJE
If the average amount of urine produced is 2 liters per day, a Mexican American consuming on average one cup of rice would therefore be consuming an absorbed dose of about 45 μg of total arsenic to produce 15.8 μg/L of total urinary arsenic.  ([45 * 0.70] / 2) = 15.8 μg/L

I assume my math and logic are both correct on this.

Point here is this.  If the total arsenic Consumer Reports found in the Martin Long Grain Brown Rice was 398 μg/Kg, consuming one cup of this rice would produce a total dose of  72 μg total arsenic.  If 70% of that is excreted in the urine as total arsenic, we would see 50.4 μg in the total urine produced in a day.  If the average amount of urine is 2 liters, this would equate to a urinary total arsenic concentration of about 25 μg/L.

What does all this math mean?  Look at it this way.  If Mexican Americans consume more rice than whites, and the average urinary total arsenic in a Mexican American is 9.29 μg/L, if Dr. Smith is correct and Urinary arsenic concentrations give a good biomarker of the absorbed dose of arsenic, since about 70% is excreted in the urine.  The exposure dose is about 28 μg for a person producing 2 liters of urine.  That's 28 μg from all sources.

Now that 70% excretion was calculate from drinking water.  It is possible that the majority of arsenic in the rice is excreted through the feces.  If that's the case, we can assume that this arsenic was not made available for harm (bladder cancer), which seems to be supported by the CDC data on rice eaters.

Since we do have evidence that rice eaters have more urinary total arsenic than non-rice eaters, we can ask the question, do those groups who are considered to consume more rice show a higher incidence of bladder cancer compared to those who do not.

Here is where that CDC report comes in handy.  It appears that Whites have lower urinary total arsenic than Mexican Americans and Blacks.  If , according to Dr. Smith's contention that "urinary arsenic concentrations give a good biomarker of the absorbed dose of arsenic, since about 70% is excreted in the urine," those with higher mean concentrations of urinary total arsenic must be consuming more food products with higher concentrations of arsenic.

Not sure about Blacks, but Mexican Americans were singled out by Consumer Reports as being rice eaters:
And certain ethnic groups were more highly affected, including Mexicans, other Hispanics, and a broad category that includes Asians.
We can assume that their higher urinary total arsenic must come from the consumption of rice.  And, if one cup is the average amount of rice consumed, that's a lot of arsenic consumed with the rice.  Remember that Consumer Reports looked at a rice serving size of 1/4 cup.

Which brings us back to "troubling," "worrisome," "cause for concern," or "potentially harmful."

You see - well at least as I see it - if a 1/4 cup serving size that exceeds the New Jersey drinking water standard of 5 ppb is considered by Consumer Reports to be "troubling," "worrisome," "cause for concern," or "potentially harmful," consuming one full cup of this rice must result in four times more "troubling," "worrisome," "cause for concern," or "potentially harmful."

As Consumer Reports sees it there will be harm if a serving is above 5 ppb.  That harm must therefore be based on bladder cancer since that is what the NRC based the slope factor on used to support New Jersey's 5 ppb drinking water standard.  Bladder cancer is also what IRIS is using for the Cancer Slope Factor - potency - they propose for arsenic.

So...if Mexican Americans and Asians consume more rice than Whites...and rice eaters have more urinary total arsenic than non-rice eaters...and the Cancer Slope Factor assume a potency whereby consuming more increase the risk harm...and that potency was used to that justify the New Jersey drinking water level of 5 ppb...and that Cancer Slope Factor, now proposed by the IRIS, is based on bladder cancer in woman...

...we would, therefore, expect to see more bladder cancer in Mexican Americans and Asians, especially in women...shouldn't we?

If those who consume rice have higher concentrations of urinary total arsenic, and there is a linear dose-response as the EPA's ATSDR contends, those who consume rice should show a higher bladder cancer incidence.

Drum roll please.....

Next post: Arsenic in Rice: Part 16 - Rice Eaters and Bladder Cancer


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Friday, October 19, 2012

Arsenic in Rice: Part 14 - Give me a "P"...Arsenic in the Urine

If you thought 13 posts on the cancer Slope Factor was fun and interesting.  You are going to love this discussion on urine.

What do you get when you ask a bunch of Mormons to pee in a cup for five days?

You get some really good data (see footnote) on the correlation between urine arsenic and the arsenic in the drinking water they consumed.

That's going to be important in a little bit.  You see, when you read the Consumer Reports articles on arsenic in apple juice and rice you start to see a conclusion being pushed.  I can speculate as to why, but I am trying to make a case based solely on the data.  Speculation is the absence of that.  Nevertheless, you have to wonder about an agenda in play here, especially when you look into the work their subject matter experts have produced.

Case in point...here is what is quoted in Consumer Reports for arsenic in rice:
“We already know that high concentrations of arsenic in drinking water result in the highest known toxic substance disease risks from any environmental exposure,” says Allan Smith, M.D., Ph.D., a professor of epidemiology at the University of California, Berkeley. “So we should not be arguing to wait for years until we have results of epidemiologic studies at lower arsenic intake, such as from rice consumption, to take action.” His studies of arsenic in public water in Chile and Argentina helped show that it causes lung and bladder cancer and other diseases.
That Smith guy Consumer Reports uses as a subject matter expert, well he is one of the players in producing the data the NAS/NRC and New Jersey used to come up with the 5 ppb.

Source

...and his work is used all over the place in the 2010 draft IRIS toxicological review of inorganic arsenic.

Source
Here is what Dr. A. H. Smith states in the Consumer Reports article:
“So we should not be arguing to wait for years until we have results of epidemiologic studies at lower arsenic intake, such as from rice consumption, to take action.” 
No?  Instead we should base it on your data which in the draft IRIS document on arsenic we are told:
  • Weaknesses include that arsenic levels were not available at the individual source level, dose response information was not provided, and only limited individual smoking history information was available (i.e., participants were asked if they had smoked cigarettes over a 1-month period in 1990). [Page 49]
  • Weaknesses include that place of residence was determined from the death certificates, which relates to residence at the time of death, and the reliance on death certificates (potential diagnostic bias). Smoking, although considered unlikely by Smith et al. (2006), is a potential confounder for this study.
Okay...okay, my goal here is not to critique Dr. Smith's work, it is instead to show how certain statements, such as "troubling," "worrisome," "cause for concern," or "potentially harmful" are not supported by what we know about the 5 ppb threshold Consumer Reports is using to declare rice to not be "troubling," "worrisome," "cause for concern," or "potentially harmful."

I do want to look at Dr. Smith's statement that we "take action now instead of waiting for and epidemiologic studies at lower arsenic intake."  Dr. Smith is an E.  I am not an Epidemiologist (though I am staying at a Fairfield Inn in Alamogordo which is right next to a Holiday Inn Express as I write this, so....).

With that in mind, I will need to use other peoples work to make the case that the evidence before us does not show a need to "take action now" which would lead to this action:
Consumers Union believes a standard for arsenic should be set for rice.
After 13 posts, I hope I have shown how the current proposed Slope Factor that leads to a "safe" threshold of 5 ppb - which is used by New Jersey for drinking water - does not mean there is harm, or unnecessary risk, when consuming rice at up to 10 μg arsenic per serving.

Okay, you may be saying, ...but what about the fact that rice eaters have higher amounts of arsenic in their urine?  Huh?  What about that???  Doesn't Consumer Reports state:
People who ate rice had arsenic levels that were 44 percent greater than those who had not, according to our analysis of federal health data. And certain ethnic groups were more highly affected, including Mexicans, other Hispanics, and a broad category that includes Asians. (CR)
So let's run with that, shall we...

According to their subject matter expert, Dr. A. H. Smith:
Urinary arsenic concentrations give a good biomarker of the absorbed dose of arsenic, since about 70% is excreted in the urine.  Excretion of arsenic in urine as a function of exposure to arsenic in drinking water. (AJE
Here is what Consumer Reports tells us:
Researchers at the Dartmouth Children’s Environmental Health and Disease Prevention Research Center in late 2011 published a small but informative study that indicated consuming slightly more than a half-cup of cooked rice per day resulted in a significant increase in urinary arsenic levels, comparable to the effects of drinking a liter of water containing the federal maximum of 10 ppb arsenic. The authors say their results suggest “many people in the U.S. may be exposed to potentially harmful levels of arsenic through rice consumption.”
I went to the Dartmouth Children’s Environmental Health and Disease Prevention Research Center's web page and looked up everything they had on arsenic.  I cannot find anything dated in 2011, but what I did look at does not state anything like "many people in the U.S. may be exposed to potentially harmful levels of arsenic through rice consumption."  Here is what their research and papers state:
  • Despite these limitations, our findings suggest that rice is a potential source of arsenic exposure in U.S. children and highlight the need to better understand the health consequences of common levels of arsenic exposure early in life. (1)
  • Our study suggests that rice consumption is a potential source of arsenic exposure in U.S. children. (2)
  • There is some evidence that high levels of arsenic exposure during childhood are associated with neurobehavioral problems as well as cancer and lung disease later in life. However, further research is needed to understand the health effects of exposures like those observed in this study. (3)
I am not in any way shape or form implying that arsenic is not a health concern.  I am making an argument that the amount of arsenic reported to be found in rice sampled by Consumer Reports is not in any way shape or form "troubling," "worrisome," "cause for concern," or "potentially harmful," if it exceeds 5 μg per serving.

Continuing on...

Have I ever mentioned how glad I am to work for a University where I have access to their library...I looked up that Dartmouth report, where I read this:
Among the roughly one-quarter of Americans who report rice consumption, the average amount of rice consumed is approximately 1 cup of cooked rice per day
So here is what we know so far:
  • Urinary arsenic concentrations give a good biomarker of the absorbed dose of arsenic, since about 70% is excreted in the urine. 
  • Rice eaters had arsenic levels that were 44 percent greater than those that do not consume rice.
  • The average amount of rice consumed is one cup.
  • Consumer reports measured the amount of inorganic arsenic in one serving of rice and found the highest level to be 9.6 μg per 1/4 cup.
Looking closely at the urine...remember, science is fun...we can start to get an idea of how much inorganic arsenic is actually being consumed.  And, with that information we can ask the question do we see an increase in bladder cancer for those rice eaters compared to the general public as a whole?

The premise here is based on this:  If arsenic increases the risk of bladder cancer (which is what the Slope Factor is based on) then those who are exposed to more arsenic (rice eaters) would show more incidence of bladder cancer.

Let's see what the data shows....


Source: Calderon RL, Hudgens E, Le XC, et al. Excretion of arsenic in urine as a function of exposure to arsenic in drinking water. Environ Health Perspect 1999;107(8):663-667.

Next post: Arsenic in Rice: Part 15 - Urine From Rice Eaters


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Saturday, October 6, 2012

Friday, October 5, 2012

Arsenic in Rice: Part 13 - It's There, You Just Can't See It.

Wow, 12 posts already, my, I do like to ramble.

And ramble on I will!  There is a reason for this rambling I do, and that is one of soundness.  I am calling Consumer Reports out on their recent report on arsenic they found in samples of rice they tested.  I am making a case that the amount of arsenic they found and printed in red does not warrant the use of the terms "troubling," "worrisome," "cause for concern," or "potentially harmful."

I could just stop at one post and call them a bunch of cotton-headed ninny muggins and be done with it.  And even though I would be right that there is not cause for concern, without supporting my contention, I would be no better then them.

Consumer Reports bases "troubling," "worrisome," "cause for concern," or "potentially harmful," because some rice exceeded a threshold:



For me to say there is no health concern at the maximum concentration of inorganic arsenic found, 9.6 ppb, means I have to show why Consumer Reports concern is not warranted.  The previous 12 posts have focused on what that threshold of 5 micrograms actually means in terms of risk as well as tried to show how exceeding it up to 9.6 ppb does not pose a health concern.  I tried to do this by  by showing how New Jersey came up with the number "5" and how it is dependent on a Slope Factor that most likely does not represent the true risk it theoretically calculates.

If exceeding 5 micrograms per serving is "troubling," "worrisome," "cause for concern," or "potentially harmful," then rice below that amount is not.  And if 5 micrograms is safe, then we assume a certain number of excess bladder and lung cancers is therefor acceptable.  But we can only accept those excess cancers at 5 micrograms if the Slope Factor they used actually reflects the real risk.  And when we look at the actual risk at low levels of arsenic in drinking water, the researchers find:
Since the NRC reports, a number of studies have been published that did not find an increase of internal cancers at low level arsenic exposure. These include Guo (2000), Steinmaus (2003), Lamm (2003, 2004), and Bates (2004), all of which found no evidence of an increase in bladder cancer rate at low-level arsenic exposure levels. Both Guo (2004) and Chen CL (2004) found no increase in lung cancer rate at low-level arsenic exposure levels.
Which means when Dr. Lamm reports:
  • An ecologic analysis of the white male bladder cancer risk in the United States found no increase over an arsenic exposure range of 3–59 μg/L (ppb).
  • Case–control bladder cancer studies found no increased risk in the United States for exposures less than 80 μg/day (ppb).
...and we take those numbers, a maximum of 59 ppb and 80 ppb, finding 9.6 micrograms in one rice serving sample will show no increased risk for bladder or lung cancer.

Dr. Lamm, Dr Honeycutt, and the National Rural Water Association lead me to conclude that the Slope Factor - used by New Jersey and the EPA in the draft IRIS document - from data presented by Morales - is incorrect and does not represent the true risk of lung and bladder cancer seen at low levels.

Not so fast, say the NRC researchers:

NRC 2001 Arsenic in Drinking Water

Which leads them to write this:

NRC 2001 Arsenic in Drinking Water

So you mean to tell me that you can calculate the risk from data collected for "Liver, lung, and bladder cancer mortality data [that was] collected from death certificates of residents in 42 villages during 1973 through 1986"....

....And you can make a Slope Factor based on arsenic concentrations in the drinking water wells "collected from wells in the 42 villages between 1964 and 1966" (1)....

...And then you tell me that you cannot calculate the low level risk from the current data available in the US because of "unknown distribution of other risk factors?"

Really?  Tell them what I think about that Col Potter:















Here is what Dr. Lamm points out:
If an ecological study in the range of interest is desired, then the data are available for analysis from US government sources. These data would obviate the need to make speculative assumptions of differences in body weight, fluid consumption, nutritional status, etc. between the study population and the US population.
And here is what the EPA is concluding should be the Slope Factor and risk for arsenic

EPA IRIS

At that Slope Factor, we would expect to see 7.3 excess cancers in 1000 (7.3E-03).

Dr. Honeycutt with the TCEQ says "horse hockey" as well:
For bladder cancer alone, the incidence risk calculated by USEPA based on final draft values for males/females is 3.1E-04 per μg/L. Therefore, based on 2 μg/L as an average drinking water concentration, the estimated bladder cancer risk for the US population would be 6.2 per 10,000 or 62 per 100,000. However, the actual occurrence of bladder cancer in the US is about 23 cases per 100,000 (males/females combined). It would take 3 times the actual bladder cancer incidence for US males/females combined to even make possible the 62 cases per 100,000 estimated due to arsenic exposure from drinking water alone. Thus, the incidence risk calculated by USEPA final draft values for bladder cancer appears to be inaccurate and overly conservative.
Okay, so I have beat the hell out of this dead horse on Slope Factor.


If I have not supported by argument that the Slope Factor is incorrect, and, therefore the 5 ppb is incorrect, there is not more evidence I can offer.  I can say, based on what I have shown in these previous 13 posts, that rice that may go as high as 9.6 μg per serving is not "troubling," "worrisome," "cause for concern," or "potentially harmful."  It is just rice.

I have also concluded this as well about how a Slope Factor for cancer risk is calculated:
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.
(Honeycutt TCEQ)


Next Post: Arsenic in Rice:  Part 14 - Give me a "P"...Arsenic in the Urine

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Thursday, October 4, 2012

Arsenic in Rice: Part 12 - Look No Closer Than Your Own Backyard

The real problem with Consumer Reports articles on arsenic in apple juice and rice is that it shows concentrations of arsenic that are not "troubling," "worrisome," "cause for concern," or "potentially harmful."

The rice report, specifically, conveys to the public that there is a risk by showing rice samples with arsenic concentrations printed in red.  This table of inorganic arsenic they found in the rice they samples is explained like this::


What message does Consumer Reports want their readers to leave with?  Should they stop consuming rice? Buy only brands without out the "red" numbers?  Throw out the rice they have in their pantries?  What should be done?

What, other than "troubling," "worrisome," "cause for concern," or "potentially harmful," will the average reader conclude when looking at those results?

This is the problem with a threshold.  Safe on one side, unsafe on the other.  What Consumer Reports and their experts are either woefully ignorant of, or are be purposely misleading, is that the New Jersey threshold of 5 ppb does not in itself mean "safe" nor does exceeding it by twice the amount, in this case 9.6 ppb (the maximum inorganic arsenic Consumer Reports detected) mean "unsafe."

That 5 ppb "limit" is nothing more than a number New Jersey wants based on the Slope Factor that shows a one in one million excess bladder/lung cancer risk of 0.003 ppb.

My point - and maybe i made it long ago - is that 5 ppb is just a number that can be obtained, it is not a number that exceeding it is "troubling," "worrisome," "cause for concern," or "potentially harmful."  It came about from a Slope Factor based on data from an ecological study from a high exposure population in Taiwan.
The Taiwanese dataset [data underlying the study Wu et al. (1989) study and the analyses in Morales et al. (2000)] has been analyzed by the NRC (1999; 2001) and the EPA]. It has served as their analytic database for estimating the risk of internal cancers from the ingestion of water containing inorganic arsenic. NRC considered that the reason for modeling with the SW-Taiwan data was that at that time there was insufficient information to assess the risk from low-level exposure and only the SW-Taiwan study had a sufficient quantity of data over a wide range of arsenic exposures that could be used for risk analysis and extrapolation. (Lamm 2005)
That same dataset is also being used EPA to lower the MCL of arsenic to 3 ppb, and it is based on the Slope Factor derived from that data.  That Slope Factor, the one that leads Consumer Reports to 5 ppb "limit" and is sending the EPA towards a 3 ppb limit, is being questioned as to its validity and the potential damage it will cause if it is adopted if it is indeed incorrect.  As Dr. Honeycutt with the TCEQ tells the EPA:
Proceeding with this SFo will unnecessarily alarm the public by giving a greater perception of harm and risk than is actually taking place.
Dr. Honeycut is not the only one who takes issue with the draft IRIS report and the Slope Factor derived from the Taiwanese dataset.  Here is what the National Rural Water Association wrote about this draft IRIS report:
High quality data from the US and elsewhere indicate much lower risks from iAs ingestion at the levels of exposure relevant for the past and current MCL, yet these studies are not used at all in the Agency’s new quantitative risk assessment because EPA focuses exclusively on the Taiwanese data.  
I know what you may be thinking: Well of course those two are opposed to a lower standard!  It's going to cost them money and effort!  Yeah, that could be the driver, but in the end, is what they are saying, their "point" sound?  Heck, even though I have no dog in this hunt, I have used 12 posts to support my point, and I got a lot more support I am going to throw out there.

Okay, so I'll give you the bias angle, is there anyone else that takes issue with the EPA and the dataset used to determine the Slope Factor?

Well I found something written by this guy named Steven H. Lamm.  He is an MD and an MPH (like me) and bills himself as a "Consultants in Epidemiology & Occupational Health, LLC. with Johns Hopkins University-Bloomberg School of Public Health Georgetown University School of Medicine."

I found a letter from him to the EPA Science Advisory Board (SAB), dated September 5, 2005.  He writes:
There are many questions regarding data quality that are raised by the above analysis. Are the diagnoses correct? Is the case count correct? Is the population ascertainment and subsequent person-year distributions correct? Is the well inventory complete and accurate? Are the arsenic measurements correct? Did the residents only drink from their village wells? Was the arsenic level constant over decades? Were the risks independent of subsequent switch to piped water both quantitatively and temporally?
What becomes troubling about the Slope Factor the EPA wants to use is that they seem to be ignoring this:
As the data to examine these questions is limited or absent, we have to accept various assumptions. We are struck with the observation that in multiple ways when the data is bifurcated, the dose-relationship differs in the two sections. We conclude that there exists within the data some additional unobserved factor(s) that influences the outcome, but has not been adequately identified or characterized. Lamm
And now the plot thickens.  Remember how the Rural Water guys said "High quality data from the US and elsewhere indicate much lower risks from iAs ingestion at the levels of exposure relevant for the past and current MCL?"  Well here is what Lamm reports to the EPA - using the same data used by the EPA:
We noted that the lower level exposure villages showed a negative slope with R2 = 0.25, which appears to be inconsistent with the general expectation of a dose-response model, though p=0.10.
The SW-Taiwan dataset reflects significant inherent geographically-based risk factor(s) which, when disentangled, reveal no significant arsenic-dependent risk for bladder and lung cancers for the low-level exposure villages.
"Disentangled,"  hehe, MPH's use funny words.

Well now...where does all this lead us?  Dr. Honeycutt complains about the noise, Dr. Lamm says the lower dose-level exposed Taiwan villagers reveal "no significant arsenic-dependent risk for bladder and lung cancers," and The National Rural Water folks wonder why the EPA is not looking at "data from the US and elsewhere indicate much lower risks from iAs ingestion at the levels of exposure relevant for the past and current MCL."

That's a good question, that last one.  Why don't we look at US exposure to arsenic and compare bladder & lung cancer incidence based on exposure?  I mean, to me, that would show if these low levels of arsenic actually do present the same degree of risk the EPA's new Slope Factor is predicting.

I mean, wouldn't current data using American's with American habits and American data on cancer make a much better study group?  Has that been looked at?  Why yes, yes it has.  According to Dr. Lamm in Environmental Health Perspectives 2006 July; 114(7): 1077–1082:
  • An ecologic analysis of the white male bladder cancer risk in the United States found no increase over an arsenic exposure range of 3–59 μg/L (Lamm et al. 2004). 
  • Case–control bladder cancer studies found no increased risk in the United States for exposures < 80 μg/day (Steinmaus et al. 2003)
Interesting...

Dr. Lamm finds:
  • A threshold-like model indicating that the bladder cancer mortality risk does not increase with exposure levels < 150 μg/L is consistent with other epidemiologic data.
  •  Cigarette smoking still remains a risk factor for bladder cancer.
So here is my take on this.  We have really, really good data on the arsenic concentration in water that is consumed.  For example:

Evaluation of Arsenic Contamination in Texas
...and we have really, really, good data on cancer

Source

So putting the two together, me thinks we would see elevated incidence of bladder and lung cancer in areas where the arsenic is highest and less in areas where the arsenic is low.  At least that data would be newer and more complete and any confounders present would be relatively the same as in Taiwan.

Makes sense to me to look here as well as there.


Arsenic in Rice: Part 13 - It's There, You Just Can't See It.

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Wednesday, October 3, 2012

Arsenic in Rice: Part 11 - Dose-response is the cornerstone of toxicology

From 2010 Draft IRIS we learn:
In response to comments from NRC and SAB, a slightly different approach to estimate cancer risks for U.S. populations is being used. In the following analysis, arsenic concentrations corresponding to an additional 1% lifetime cancer incidence (effective dose; ED01 values) above “background” are derived for each endpoint [bladder/lung cancer].

A little primer on EDs...
NRC

 Using the Morales et al. data, the EPA IRIS reports:
Depending on the model used and the comparison population used in the analysis, the effective dose at the 1% level (ED01) estimates ranged from 21 to 633 ppb for male bladder cancer, and from 17 to 365 ppb for female bladder cancer. The lung cancer risk for males was found to be slightly higher than the bladder cancer risk, with ED01 estimates ranging from 10 to 364 ppb.  The risk for female cancer tended to be higher than that of males for each cancer type. For lung cancer, female ED01 estimates ranged from 8 to 396 ppb.
What this means is that the concentration required to obtain an additional 1% cancer incidence for male bladder cancer is either 21 ppb or 633 ppb, depending on what model you use.

Why this is important, this variation of 21 or 633 needed to get the same result - an additional 1% cancer incidence for male bladder cancer, shows up here (draft IRIS):
Also derived are lowest effective dose (LED01) values, which represent the lower confidence limits on the dose corresponding to a one percent lifetime incidence risk in the U.S. population.  [R]isk estimates are derived based on a linear extrapolation from the points of departure (LED01s for lung, bladder, and combined cancers) because the [Mode of Action] MOA for inorganic arsenic is unknown.
What this means, if I am understanding it correctly, is that depending on what model is used, an ED01 is produced.  This ED01 is a statistically derived number and will have a 95% Confidence Interval produced, and the lowest number of that range will produce the LED01.  That number is what is used to produce the Slope Factor which is used to produce the risk of excess cancers which is then used to determine the "safe" dose - the line in the sand - the threshold.

You can see these values, the ED01 and LED01, in Table 5-3:

Draft IRIS Page 131
I can't really do the math here any justice, but what you can see from this table is that the LED01, which is the lower confidence interval, and is used to produce the line (linear extrapolation) from which the Slope Factor is determined, which represents the theoretical potency, which determines the risk (1 in 1,000,000 or 1, 10,000) was based on the lower values spat out by the different models used to calculate the ED01.

...in the hous that Jack built!

Confused?  Me too, kind of.  What this shows is that when calculating the Slope Factor the lowest concentrations of arsenic that showed came out of the models were used.  This being the case, with a range of ED01 anywhere from 21 ppb or 633 ppb, for example, means that the risk calculated from these Slope Factors are extremely high.  With that in mind, a serving of rice that has inorganic arsenic 5 ppb over the 5 ppb threshold established by New Jersey is probably no more hazardous for lung/bladder cancer than if it was 5 ppb below that value.

Because the Slope Factor is dependent on a linear extrapolation of the LED01 the numbers used to calculate the ED01 must accurately reflect an additional 1% lifetime cancer incidence above “background.”  

EPA reports in the draft IRIS that these numbers were from 21 ppb or 633 ppb for male bladder cancer depending on what model was chosen.  How far of, then, the Slope Factors are from reality (actual incidence of excess bladder/lung cancer) is anyone's guess.

What there is no guessing about is this.  Eating a serving of rice containing 9.6 μg every day - for 70 years - would not be "troubling," "worrisome," "cause for concern," or "potentially harmful."

But don't take my word for it.  Let's look at what the National Rural Water Association wrote about this draft IRIS report:
The most likely  [Mode of Action] MOA for arsenic correspond to sublinear dose-response models, which when fitted to the available data, suggest much lower cancer risks (by a factor of up to 200) at exposure levels at or below the MCL when contrasted to the EPA’s estimates from the linear model.
..and:
Since the MOA could not be established, the EPA is continuing in its application of the linearized, non-threshold model of dose-response, despite a lack of evidence of increased cancer incidence at typical environmental levels of exposure in the U.S.
...and:
The data of Morales et al. for bladder cancer in a Taiwanese population has been graphed. The arsenic concentration is in μg/L, and the y-axis is lifetime probability of bladder cancer. The solid line is the best-fitting linear model::



Which brings us back to Dr. Honeycutt with the TCEQ:
USEPA used lung and bladder mortality data from Morales et al. (2000) for the dose-response assessment for the final draft SFo.  Morales et al. (2000) 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.”
Dr. Honeycutt responds:
To say that there is “noise” in the SMRs over the eight exposure categories is an understatement. 
Dose-response is the cornerstone of toxicology, but the lung and bladder mortality data (SMRs) from Morales et al. provide a poor basis for dose-response assessment as a dose-response is not apparent and not monotonic. 
Breaking the data down into the form of age-specific person-years at risk and cancer deaths does not improve the basis for dose-response assessment; it only obscures the lack of a good dose-response which is readily apparent from examination of the SMRs.

I have whipped this dead horse on the Slope Factor as much as I can.  Let's look at it another way.  Do we see the number of bladder cancers estimated by the Slope Factor derived from the Morales et al. data?

I addressed this once before in a previous post.  I'll do it again with a bit of a different spin.


Next Post: Arsenic in Rice: Part 12 - Look No Closer Than Your Own Backyard

Tuesday, October 2, 2012

Arsenic in Rice: Part 10 - Everyone loves Morales et al.

In my last post, I wrote that eating one serving of rice containing 9.6 μg of inorganic arsenic - every day - for 70 years - would present a risk of 7 in 1,000 excess bladder/lung deaths for females.  This, I wrote,  was 3 excess bladder/lung cancers more than what the "most protective level" of 5 μg/L would theoretically produce.

I want to be clear here and make sure that my point is not being misconstrued.  I am not making the point that 5 μg is not the "most protective level" and that it should be lower, say 0.003 μg/L.  On the contrary, what I am trying to get across is that 5 μg/L is not an appropriate number to establish a threshold.  Not because it is too high, but because it does not imply "safe" and "unsafe" like Consumer Reports and their experts are wanting us to conclude.

That number -  5 μg/L - is just a number to support getting the arsenic concentration down as low as we can to the stated goal of "zero."  If we understand environmental causes of cancer correctly, then anything above zero is a risk.  This does not have to paint us into a corner, but it does.

Why?  Because Consumer Reports implies that a serving of rice exceeding 5 μg/L is "troubling," "worrisome," "cause for concern," or "potentially harmful."  They assume that 5 ppb is "safe" and that above that is "unsafe."

"Troubling," "worrisome," "cause for concern," or "potentially harmful," was used by Consumer Reports to convey "unsafe" for two reasons in my opinion:
  1. They do not understand what New Jersey's 5 μg/L arsenic in drinking water represents, and;
  2. They are pushing a zero threshold agenda
Again, so that my message is not misconstrued:
If Consumer Reports considers New Jersey's arsenic standard of 5 μg/L the "safe" threshold for rice....and;
Rice that has up to 5 μg/L of inorganic arsenic per serving would not make it "troubling," "worrisome," "cause for concern," or "potentially harmful."....and;
New Jersey considers 5 μg/L to be the "most protective level"...and;
Based on the EPA Oral Slope Factor derived from data produced by Morales et al,  5 μg/L would result in a risk of 3.6 excess bladder/lung cancers in 1,000....
Then Consumer Reports agrees that a risk of 3.6 out of 1,000 excess bladder/lung cancers is most protective of the population that consumes one serving of rice per day for 70 year.
You can see why I take issue with the conclusions presented by Consumer Reports and the experts.  They imply that on this side it is "safe" and on that side it is "unsafe."  It is neither.  Which is why using an MCL should never be used to present to the public a comparison of the ranges where the MCL is exceeded.

Consumer Reports is wrong, wrong, wrong, on this.  It does not provide a "yardstick" - it provides the public nothing but confusion and concern.  Which is exactly the point Dr. Honeycutt with the TCEQ was driving at:
Proceeding with this SFo [Oral Cancer Slope Factor from Morales et al.] will unnecessarily alarm the public by giving a greater perception of harm and risk than is actually taking place.
By using red ink in their tables, as well as using the terms "troubling," "worrisome," "cause for concern," or "potentially harmful," Consumer Reports has alarmed the public by supporting a greater perception of harm and risk than is actually taking place.  This is inexcusable for a magazine of this caliber and extremely unsettling that their toxicological experts were not knowledgeable of this fact.

So let's get back to it shall we.  Is inorganic arsenic in a serving of rice that is greater than 5-ppb but less than 10 ppb "troubling," "worrisome," "cause for concern," or "potentially harmful?"

Only is you think an increase of risk from 3.6 in 1,000 to 7 in 1,000 is substantial enough.  And that increase is also dependent on consuming a serving of rice each day for 70 years with 9.6-ppb inorganic arsenic (we will ignore for now the fact that the average concentration of arsenic found in all the samples was below 5 ppb and assume that each day the rice contains the maximum level found - 9.6 ppb).  Oh, and another thing we need to consider is that the risk, from 3.6 to 7, is dependent on the Oral Slope Factor that was developed using data from Morales et al. (2000).

Let's look at that Morales et al. data, shall we?  First off, I am not trying to make a case that the data is - or is not - valid.  I will assume it is.  What I want to show is how much uncertainty there is in the final Oral Slope Factor that was calculated.  This uncertainty makes the increase in risk from 5-ppb to 10-ppb impossible to calculate with any degree of accuracy.  Yet, there it is, used by Consumer Reports to draw a line in the sand, a threshold held up as sacrosanct.

Here is what the EPA has to say about the data they used from Morales et al.:
The calculation of cancer risks from the Taiwanese epidemiological data was performed using Excel workbook files. The files contained the input data for the dose-response models and spreadsheets to accept user-specified inputs, perform calculations, and summarize outputs from the assessment. Input data included male and female lung and bladder cancer mortality and person-years at risk (PYR) data for arsenic-exposed populations from 42 villages obtained from Morales et al. (2000), village water arsenic concentrations (minimum, median, and maximum data sets), and southwest Taiwan and all Taiwan reference population mortality and PYR data.
You can download those Excel files here.  Digging a bit deeper, we get this from the EPA in the IRIS draft report:
The Morales et al. (2000) ecological investigation re-analyzed data originally reported by Chen et al. (1988a, 1992) and Wu et al. (1989) from 42 villages in the arseniasis-endemic region of southwestern Taiwan by considering the number of liver, lung, and bladder cancer deaths.  Morales et al. (2000) used a generalized linear model (i.e., Poisson distribution) and the multistage-Weibull models to determine lifetime cancer risk estimates. Liver, lung, and bladder cancer mortality data were collected from death certificates of residents in 42 villages during 1973 through 1986.
Okay, they collected data from death certificates...
Drinking water samples had been collected from wells in the 42 villages between 1964 and 1966.
...and Morales et al. used sample data from 1964 through 1965.  Well...okay...
SMRs [standard mortality ratio] were used to summarize the observed patterns of mortality in the collected data. Morales et al. (2000) selected two comparison populations (the Taiwanese population as a whole and a population from a southwestern region of Taiwan) to account for urban versus non-urban populations differences.
...okay...standard toxicological stuff...
Although a non-significant trend was observed in the combined cancer analyses with respect to age, there was no observed tendency in liver, lung, or bladder SMRs with respect to age. This suggests that there is no age dependency on the risk ratio.
...okay, that takes out one confounding issue...
The Morales et al. (2000) investigation results showed that exposure-response assessments were highly dependent on the choice of the analysis model and whether or not a comparison population is used in the analysis.
And the reason?....
One possible explanation for this observation is the inherent uncertainty associated with the limitations of an ecological study design. Depending on the model used and the comparison population used in the analysis, the effective dose at the 1% level (ED01) estimates ranged from 21 to 633 ppb for male bladder cancer, and from 17 to 365 ppb for female bladder cancer. The lung cancer risk for males was found to be slightly higher than the bladder cancer risk, with ED01 estimates ranging from 10 to 364 ppb. The risk for female cancer tended to be higher than that of males for each cancer type. For lung cancer, female ED01 estimates ranged from 8 to 396 ppb.
Wait...the number used to calculate the Slope Factor is based on the 1% effective dose (ED)...and that number ranges from 21 to 633 ppb, 17 to 365 ppb, 10 to 364 ppb, and 8 to 396 ppb for the two cancers in men and woman?

And they calculated a Slope Factor that was used to support a standard of 5 ppb for arsenic in drinking water.  And Consumer Reports wants me to believe that exceeding 5 ppb up to a maximum of 10 ppb in a serving of rice is "troubling," "worrisome," "cause for concern," or "potentially harmful?"

Really...are you serious Consumer Reports?  You are basing it on a threshold for arsenic in drinking water that uses data with this in play:
Weaknesses include the ecological study design (i.e., there were no individual monitoring data and individual exposures were not available) and the fact that potential confounders such as smoking, dietary arsenic, and the use of bottled water (U.S. population) were not controlled for in the analysis.
And in spite of these weaknesses, the EPA and New Jersey, and the NRC marched forward with a Slope Factor.  Which is exactly why Dr. Honeycutt with the TCEQ made this statement:
Proceeding with this SFo will unnecessarily alarm the public by giving a greater perception of harm and risk than is actually taking place.
So how "off" can this excess cancer risk be?  Glad you asked that, now I can move on to the 11th post.


Next post:  Arsenic in Rice: Part 11 - Dose-response is the cornerstone of toxicology

Monday, October 1, 2012

Arsenic in Rice: Part 9 - The Broad Shoulders of Morales et al.

Consumer Reports has drawn a line in the sand regarding the amount of inorganic arsenic they found in a bunch of different rice samples they collected and analysed.


Consumer Reports uses the New Jersey threshold - MCL - for water, 5 μg/L.  That threshold was based on analysis by the NRC on data proved by Morales et al.
Morales, KH; Ryan, L; Kuo, T-L; et al. (2000) Risk of internal cancers from arsenic in drinking water. Environ Health Perspect 108:655–661.
5 μg/l was what the EPA originally proposed an arsenic standard but in January 2001, it was changed to 10 μg/l.  The consensus of EPA, was to get the MCL down to 5 μg/L.  Enter a new President and a new director of the EPA, and in 2010,  IRIS issues an "External Review Draft" called the "Toxicological Review of Inorganic Arsenic (Cancer).  It is important to not here, that this draft has been in the making since 1999.  A different administration views the risk differently.  Which is one of my points.  How should we quantify risk for water and rice that is reasonable, prudent, and...well...reflects reality.

These cancer risks are based on a Slope Factor, which is "the theoretical cancer potency estimate for humans." (CalEPA)

I'm going to argue that this "theoretical cancer potency estimate" paints us into a corner when attempting to communicate the risk of exposure, especially the risk to a chemical suspected of causing cancer in humans.

It is not that it is "theoretical" that I take issue with, it is that the number it derives - the excess cancer risk - is not a threshold whereby exceeding it by 1, 5, or 10 ppb becomes "troubling," "worrisome," "cause for concern," or "potentially harmful" as Consumer Reports points out that it does.

If I am going to support my conclusion that the rice is "safe," I am going to have to show why exceeding the 5 ppb threshold is not harmful.  The thing is, I can't do that.  I have been painted into a corner that says there is no safe exposure to a carcinogen.  This corner is also where New Jersey finds itself when it says the drinking water concentration that results in a one-in-one-million excess lifetime risk meets their law as an acceptable risk.

This corner gives us no where to go based on this thinking.  This is why Dr. Honnycutt with the Texas Commission on Environmental Quality made this statement to the EPA about their 2010 External Review Draft on the  "Toxicological Review of Inorganic Arsenic (Cancer)."


Like I said previously in my past posts, exceeding 0.003 μg/L increases the risk.  Accepting the threshold of 5 μg/L as the "most protective level" assumes that one then accepts a new risk threshold of 2 excess cancers per 1,000 (2E-03) based on consuming two (2) liters of water at 5 μg/L.  This is based on a Slope Factor that I calculated based on a 1 in 1,000,000 risk at 0,003 μg/L (I assumed 2 liter/day).

Let's instead look at the risk using the new and improved draft IRIS values, which are based on an Oral Cancer Slope Factor for women:

2010 Draft IRIS Page 150-151

Based on the IRIS data, which is based on data from Morales et al. (2000), drinking on liter of water, or consuming one serving of rice (Consumer Reports) with 0.14 μg/L (ppb)  would present an excess cancer risk for lung and bladder in women of 1 in 10,000 (10-4, the acceptable risk for carcinogens in water.)

Using that same data, consuming one serving of rice that had the highest concentration of inorganic arsenic (9.6 μg)  for a lifetime - 70 years- would see an excess cancer risk of  7.3 in 1,000 in women.

Looking at it another way, if the "unit risk" for arsenic is 7.3 in 10,000 for one μg of arsenic in water, 10 μg would increase that risk 10-fold - 73 in 10,000 or 7.3 in 1,000.

If we can accept that unit risk, which was derived from data provided by Morales et al. (2000), then we can figure out what the excess cancer risk is at New Jersey's "most protective level" of 5 μg/L:
5 μg/L x 7.3E-04 = 36.5E-04 or 3.6 in 1,000.

Now we can have some fun....

According to Consumer Reports:
Using the 5-ppb standard in our study, we found that a single serving of some rices could give an average adult almost one and a half times the inorganic arsenic he or she would get from a whole day’s consumption of water, about 1 liter.
Therefore, one serving of rice that contained the maximum concentration of inorganic arsenic detected, 9.6 μg:


...would present a risk of 7 in 1,000 excess bladder/lung deaths for females - which is 3 excess bladder/lung cancers than what the "most protective level" of 5 μg would theoretically produce.  This is all based on the following assumptions:
  • The female weighs 70 kg.
  • The female eats one serving of rice containing 9.6 μg inorganic arsenic - every day - for 70 years.
  • The female gets bladder or lung cancer.
  • The female dies from bladder or lung cancer.
All of those assumptions must be met to get an excess cancer risk of 7 in 1,000.  If she was to consume one serving of rice were with 5 μg of inorganic arsenic - every day - for 70 years, we would see an excess cancer risk of 3.6 in 1,000 which Consumer Reports tells us is at the "most protective level."

And, even if all of those assumptions play out, that excess cancer risk is dependent on a Slope Factor that was developed from data produced by Morales et al.


Next post: Arsenic in Rice: Part 10 - Everyone loves Morales et al.


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