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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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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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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