May 19 2010

Pesticides and ADHD

A recent article published in the journal Pediatrics links exposure to certain types of organophosphate pesticides with ADHD.  This is a reasonable study and the results should be taken seriously, but as always they need to be put into context – something most media outlets are failing to do.

First – the study itself – here are the methods:

Cross-sectional data from the National Health and Nutrition Examination Survey (2000–2004) were available for 1139 children, who were representative of the general US population. A structured interview with a parent was used to ascertain ADHD diagnostic status, on the basis of slightly modified criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.

They looked at the results of spot urine tests (a one time urine sample) for six different organophosphate metabolites, and found that two of them correlated with a statistically significant higher chance of  meeting criteria for ADHD.

One hundred nineteen children met the diagnostic criteria for ADHD. Children with higher urinary dialkyl phosphate concentrations, especially dimethyl alkylphosphate (DMAP) concentrations, were more likely to be diagnosed as having ADHD. A 10-fold increase in DMAP concentration was associated with an odds ratio of 1.55 (95% confidence interval: 1.14–2.10), with adjustment for gender, age, race/ethnicity, poverty/income ratio, fasting duration, and urinary creatinine concentration. For the most-commonly detected DMAP metabolite, dimethyl thiophosphate, children with levels higher than the median of detectable concentrations had twice the odds of ADHD (adjusted odds ratio: 1.93 [95% confidence interval: 1.23–3.02]), compared with children with undetectable levels.

There are solid results, but it should be noted that the lower end of the confidence interval (1.14 and 1.23) are only slightly greater than one, which represents only a small increase in risk. But they are statistically significant.

To put this into perspective, however, this is a correlational study only and cannot be used to conclude cause and effect. It may be possible, for example, that children with ADHD engage in behaviors that expose them to more organophosphates.

Other weaknesses acknowledged by the authors include the fact that exposure was determined by a single spot urine test – which may not reflect long term exposure. Organophosphates are generally cleared by the urine in 3-6 days.

I also noted that the prevalence of ADHD in this study, 12%, is about twice the 4-7% found by other studies. This could reflect a hidden bias in the data collection methods.

Regarding plausibility, a possible link between organophosphates and ADHD is a mixed bag. There is basic science plausibility in that organophosphates do have neurotoxicity, and specifically inhibit acetylcholine function which is involved in memory and attention.

On the other hand, toxicity is also related to dose, so the real question is are the doses detected above or below toxic levels. The EPA insists they are below safe levels, but critics contend that chronic low levels of exposure have not been adequately studied. Of course – you can always make this claim when the data does not show toxicity.

For epidemiological studies, where correlation alone can be concluded, in order to infer cause and effect we would want to see multiple different lines of epidemiological evidence. For example – are there differences in ADHD incidence in different regions and countries depending on organophosphate exposure, or over time. It has been noted that the EPA has decreased organophosphate use in the last five years but we have not seen a corresponding decrease in ADHD diagnoses.

Conclusion

This study is sufficiently rigorous that it should be taken seriously – which means that it should lead to further research.  Specifically, prospective studies including longitudinal sampling of urine for organophosphate metabolites should be done. There are also many follow up epidemiological studies that can be done, as I mentioned above, specifically looking for correlations between exposure and ADHD. Eventually we should be able to triangulate to a reliable answer.

Meanwhile – how should we respond? We often have to make decisions in medicine and public health with imperfect data, and the precautionary principle is a reasonable guide. So even though considerable doubt remains as to what, exactly, the relationship is between organophosphate exposure and ADHD, we may want to reduce exposure in the meantime just to be on the safe side.

The EPA, at least in this country, has the job of reviewing the data and suggesting policy for safe use and levels of exposure. They have been decreasing levels of organophosphate exposure recently, and perhaps will want to continue this trend.

For consumers, two options have been proposed (other than just doing nothing and waiting for more research) – assuming you want to minimize your exposure to pesticides in general. The first is simply to wash your fruits and vegetables thoroughly. This does significantly reduce (but not eliminate) pesticide exposure. If you want to go the extra step, you can wash them with a small amount of dish washing detergent. Some have suggested using vinegar and hydrogen peroxide followed by a thorough rinse, but I have not seen data to show that this is superior.

The other method is to buy organic produce, and many people do for this reason. However, this option is controversial for several reasons. First, organic produce is more expensive – it’s certainly cheaper to just wash your produce. Also, organic farming  often uses organic pesticides, and we should not assume that they are any safer. And there may be unintended consequences from massive shifting to organic farming – such as the ability to produce enough food with these methods, and higher costs may reduce consumption of fruits and vegetables, which could have more adverse health consequence than the alleged benefits of reducing pesticides.

I know that the organic farming controversy is a complex topic, and I am not trying to cover it in any detailed or thorough manner today – perhaps for another time (i.e. I don’t have time to get dragged into a long discussion about this in the comments). I am simply bringing up the points that people consider. If you want to buy organic to reduce pesticide exposure, that is reasonable and I am not criticizing that option – just pointing out that this is a complex and still controversial topic.

Like much good research, this study raises more questions than it answers. I think this does justify further research. It is unfortunate, however, that much of the press coverage is treating this study as if it is definitive. The link between pesticides and ADHD is now in the public consciousness, whether or not future research will show the link to be real or causative.

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27 responses so far

27 Responses to “Pesticides and ADHD”

  1. passionlessDroneon 19 May 2010 at 11:12 am

    Hi Stephen Novella –

    Nice write up. Thank you.

    I think it might be of interest to have a study that tried to detect metabolites as the result of either thorough washing versus organic.

    We do have a few studies which claim to show that a switch to an organic diet results in a drop in some metabolites.

    http://www.ncbi.nlm.nih.gov/pubmed/18414640

    It would be nice to see a comparison with extra good washing.

    - pD

  2. Steven Novellaon 19 May 2010 at 11:29 am

    I saw this study is also – I think it is reasonable to conclude at this time that using organic produce reduces exposure to organophosphates. But two questions remain:

    Will washing produce similar reductions?
    Are there any health benefits to the reductions?

    Again- with incomplete information, it’s a judgment call.

  3. Ashon 19 May 2010 at 11:37 am

    I’ve seen some media articles spinning this study to support residential pesticide use bans, even though the pesticides in question are agricultural, not as far as I know used for residential applications. Often the media and a lot of environmental groups lump all pesticides together, even though they cover a huge range of compounds, and I’ve seen at least one study that estimates over 99% of total pesticide exposure is from naturally occurring pesticides produced by the plants themselves (most of which haven’t been studied at all, and of those that have been studied around half show evidence of carcinogenicity).

    My take on some related issues:
    http://ashartus.wordpress.com/2010/04/29/the-natural-safe-fallacy/
    http://ashartus.wordpress.com/2010/04/21/pesticide-bans/

  4. locutusbrgon 19 May 2010 at 11:37 am

    I am so glad you looked into this Steve.
    After the study was discussed in the news I researched and found the pediatrics study. My analysis was similar. I next thought I wanted to know your impression as a neurologist. I was biased and went with a very critical eye because I feel the news never gets any medical issue correct.In addition it is my opinion that ADHD has become a garbage pail diagnosis, where non-specialists are commonly tagging and treating individuals without rigorous diagnostic criteria. My evaluation of the research had the same methodological impression as yo. The repporting, as usual, is treated as conclusive instead of correlational and interesting. I contacted the local news agency and pointed out the facts and the sensational false impression they gave. No response yet. Still I was not familiar with Organophosphate risks or body of research. I wanted to ask you as a neurologist the plausibility of such a claim. You were quick to address that and I appreciate it.
    Given that you are a neurologist I wanted your take on ADHD as whole. I explored your blogosphere yesterday but did not hit upon any specifics. I know they are revamping DSM-IV to V. My impression is overall sloppy diagnosis stratification. Poor evaluation or adjustment to behavioral problems and psychosocial issues. Easier to treat with medications than to deal with psychosocial issues. Mostly over-diagnosed, to be precise, mis-diagnosed. Interested to hear your thoughts on ADHD as a whole. Based on the pediatric study I think they did due diligence to properly stratify and diagnose ADHD and it was supported by matching average population incidence.
    Steve P.
    Rhode Island

  5. SpicyCupcakeon 19 May 2010 at 11:51 am

    Thank you! I did not have the knowledge base or time to research this when it started getting linked on facebook. Worried mothers and people who look for every chance to push organic living, were going wild about it. All I could do is point out that many pesticides can be eliminated through proper rinsing of produce.

    In your reply to PD, I was reminded of the White House report that came out a couple of weeks ago that seemed to say we need to look into the overwhelming threats in environmental causes of cancer. Their argument for that seemed to be an argument from ignorance. “We don’t know enough to say there are higher risks than we suspect, so there must be enormous risks!” Prior to this report I believed we should be looking at the environmental effects of what humans put out.

    The questions I have are, what do you think about coming out with reports that show a lack of data and express a conclusion of overwhelming danger in it as a way to bring money and attention to a valid line of research? Does that in some way undermined the integrity in the eyes of their peers or is it standard practice? In research such as the effect of pesticides on ADD or Cancer, is there a tendency to work together for funding on both or are the questions so mutually exclusive that it is not likely for cancer researchers to see this result and use it to get their own funding? I’m ignorant of the inner workings of the funding process.

    I know the answer is likely no since you take issue with this as well, but can we keep the media from reporting these exploratory studies in a way that scares the crap out of the average person? The last thing we need is a rash of parents NOT feeding their children fruits and vegetables as a way to avoid conditions like ADD. There are enough barriers to healthy foods in our society.

    Keep up the great work!

  6. SpicyCupcakeon 19 May 2010 at 12:03 pm

    # locutusbrg
    This will be anecdotal, but I will say that one source that has occurred, schools are making these diagnosis. Friends of my were told by elementary school administration that if they do not get their child onto ADD medicine they would not allow them back in school and would be forced to call child services. At different points they have been told, as well as others who went to some of the local schools, that if they don’t do this now their child will be a failure and it will be the parent’s fault. Faced with that, you have parents demanding their kid be given the medicine the elementary school told them would save the rest of their child’s life.

    This is by no means representative of all schools, and I do not know that it is a major problem across the country. I do know it occurs in the elementary schools in lower income areas in my city. From a lay person’s vantage point ADD looks more and more like a daycare diagnosis. Things that would have been considered regular child behavior make teachers and parents look to “fix” the child. It upsets me greatly.

  7. Calli Arcaleon 19 May 2010 at 12:13 pm

    Also, organic farming often uses organic pesticides, and we should not assume that they are any safer.

    One organic pesticide (not sure how often it is used) with similar effects is pyrethrin. It’s 100% natural — made from the chrysanthemum — though synthetic versions are available as well. I was moved to research it better after a door-to-door salesman tried to convince me to hire them to scattered pyrethrin pellets all over my yard. (Though frankly, I’m not going to hire an exterminator who a) doesn’t know what an arthropod is, b) thinks pyrethrin kills by dehydrating insects, c) thinks a tick is an insect, and d) thinks ticks live in communal hives. Yeah.) Turns out, it’s a neurotoxin, has killed mammals (and there are even cases of fatal poisoning in humans), can provoke asthmatic responses, and is pretty damn dangerous to aquatic life. (My neighborhood drains are festooned with “DRAINS TO LAKE” signs, so I’m not real enthused about using pyrethrin indiscriminately.)

    So organic pesticides aren’t necessarily any safer; I am very reluctant to suggest a shift to an all-organic diet, as I’m unconvinced it would solve the problem.

    Another interesting thing to study would be whether organophosphates or other pesticides are more or less of a problem on different fruits and vegetables. Potatoes, for instance, are underground; they are not directly exposed, but would pick up (and concentrate) anything found in the groundwater. Lettuce and broccoli will have lots, but may not be easily washed (especially the broccoli). Bananas — does it penetrate their thick skins? Nobody eats the skin, after all. Apples — is there a difference between eating peeled and unpeeled apples? Waxed and unwaxed? Can the processing plants (who pack the stuff up for shipment to grocers) do something more to clean off the residue?

    I think the reverse causation is definitely something that needs exploration. ADHD is known to run in families. (It definitely runs in mine!) People with ADHD are probably more likely to forget to wash their produce before eating it, which may expose them to more pesticide residue.

    If nothing else, I think this is a good reminder to us all to wash our fresh produce. Pesticides are only one reason; there’s also germs to think about. I would love to see research into the most practical ways to effectively clean food.

  8. HHCon 19 May 2010 at 12:57 pm

    I used to go to farmers’ markets locally and talk with the farmers about organic farming vs. traditional farming. One Marengo farmer became a convert to organic methods after his neighbor exposed to him to crop dusting and he seizured in the field. He died of cancer.

  9. daedalus2uon 19 May 2010 at 12:58 pm

    I would be very careful in using dish washing detergent to increase pesticide residue removal. Many (if not most) dish washing detergents are now anti-microbial and contain triclosan, a synthetic chlorinated organic compound. Triclosan is an endocrine disrupting compound.

    http://en.wikipedia.org/wiki/Triclosan

    Triclosan is quite hydrophobic and has an log octanol-water partition coefficient of 4.76 and it has a tendency for bioaccumulation. When washing vegetables with a solution containing triclosan, the triclosan would likely partition into the lipids on the vegetables.

    When washing hydrophillic things (like ceramics), there shouldn’t be much accumulation. The main ingredients of dish washing detergents, soaps, surfactants, sulfonated hydrocarbons are (very likely) completely harmless.

    As an aside, there has been no benefit demonstrated from household use of any cleaning products containing triclosan. I try to avoid them as much as possible.

  10. Rikki-Tikki-Tavion 19 May 2010 at 2:33 pm

    A typical case of this:
    http://www.phdcomics.com/comics/archive.php?comicid=1174

  11. Fred Cunninghamon 19 May 2010 at 4:11 pm

    There was a report a while back that linked fetal exposure to pyrethrin (from mothers using head lice shampoo) to autism. I haven’t seen any follow up but the report did have some plausibility.

  12. Sharkboyon 19 May 2010 at 4:19 pm

    Interesting article on ADHD which I read on the same day as this article from Christopher Hitchens’ evil (not twin) brother Peter:

    http://hitchensblog.mailonsunday.co.uk/2010/05/the-adhd-fantasy-posted-once-more.html.

    Even though I take things he writes with a pinch of salt, his was an interesting and persuasive argument about whether the condition actually existed. I wonder if you could do a segment on the SGU or on the blog dealing more generally with ADHD, whether it exists or whether it’s overdiagnosed.

  13. VRAlbanyon 19 May 2010 at 5:20 pm

    “Another interesting thing to study would be whether organophosphates or other pesticides are more or less of a problem on different fruits and vegetables”

    I work for a state agency that participates in a USDA program to collect data about pesticide levels in commonly consumed fruits and vegetables, and also in drinking water.

    http://www.ams.usda.gov/AMSv1.0/ams.fetchTemplateData.do?template=TemplateC&navID=PesticideDataProgram&rightNav1=PesticideDataProgram&topNav=&leftNav=&page=PesticideDataProgram&resultType=&acct=pestcddataprg

    I’m only a tech, and I will tell you right now that I’m not good at summing up all the data, but the information you are wondering about is available to the public.

    Here’s the latest report with all the data collected in 2008.

    http://www.ams.usda.gov/AMSv1.0/getfile?dDocName=STELPRDC5081750

    Hope that helps!

  14. Minon 19 May 2010 at 7:30 pm

    When I looked at this yesterday, the two things that stood out to someone who is non-medically educated were:

    1) It depends on the parents to diagnose the children. I don’t know how accurate that is.

    2) While the initial sample is large (1139), the comparison sample is very small. They said 94% had detectable pesticides. That means they could only compare with 6% of that group: 1139×0.06 = 68. That seems awfully small.

  15. ccbowerson 19 May 2010 at 9:29 pm

    Min –
    This type of study does not just compare a pesticide detectable group with a nonpesticide group. Take a look at the study design again.

    On another note, I wonder about the effectiveness of washing with water on removing pesticide residues. Since pesticides have varying degrees of hydrophillicity I’m sure it varies. Also what about the impact of wax on creating a barrier to removal for hydrophobic residues. Also not all foods benefit much from being organic since they do not have much pesticide residues in their nonorganic forms. (broccoli, bananas, onions etc)

    -Even for the fruits/vegs that have large differences in pesticide levels between organic and nonorganic, I wonder what happens to those differences after washing. Since that is how most people eat their fruits and vegetables that is the real way to look at it.

  16. tmac57on 19 May 2010 at 10:00 pm

    Rikki-Tikki-Tavi-Thanks for the cartoon. As Homer would say “It’s funny ’cause it’s true!”

  17. zntneoon 19 May 2010 at 10:50 pm

    I was discussing this stuff on facebook just today and got called a “big ag shill”

  18. Minon 19 May 2010 at 11:08 pm

    ccbowers-

    Actually, from reading the below article, that’s exactly how I read it:

    http://news.yahoo.com/s/ap/20100517/ap_on_bi_ge/us_children_pesticides

    “The new findings are based on one-time urine samples in 1,139 children and interviews with their parents to determine which children had ADHD. The children, ages 8 to 15, took part in a government health survey in 2000-2004.”

    “In the body, pesticides break down into compounds that can be measured in urine. Almost universally, the study found detectable levels: The compounds turned up in the urine of 94 percent of the children.”

    “The study dealt with one common type of pesticide called organophosphates. Levels of six pesticide compounds were measured. For the most frequent compound detected, 20 percent of the children with above-average levels had ADHD. In children with no detectable amount in their urine, 10 percent had ADHD.”

    Am I wrong in how I am interpreting it?

  19. ccbowerson 20 May 2010 at 1:38 am

    Min – I was only trying to say the study was more than just what youe described, but involved several different types of pesticide metabolites at varying levels, not just comparing any detectable versus undetectable.

    The media doesn’t give proper weight to this study. It is limited in what you can draw from it. It is not really designed to show a causal relationship…not even close. It is not prosective. It uses self reporting over 1 year to determine ADHD diagnostic status and correlates that with a one time measurement of metabolites. The levels of metabolites in the urine maybe representative of long term exposure, or they may be not.

    If the measured metabolites are highly variable over time they are not good surrogate markers for long term exposure. How variable the levels are would relate to the sources of exposure to pesticides. The fact that the half-lives for these compounds are fairly short also conflicts with the idea that these are good surrogate markers. This is analogous to correlating someone’s weight with their hunger level at a given point in time. Even if there is a relationship between weight and appetite, a single hunger level is not a good marker.

    I’m not saying that this is not a useful study, its just that the interpretations from it are too limited and subtle for the media to be able to report it accurately. People are already worried about all the wrong things… this just adds to it.

  20. ccbowerson 20 May 2010 at 1:54 am

    ‘I was discussing this stuff on facebook just today and got called a “big ag shill”’

    Were you praising the media coverage? At least then the comment would have some consistency to it. I assumed you then pointed out the “Big Ag” makes most of the organic crap they buy, and that the logo of the nice simple couple and their mule is called marketing.

  21. M. Davieson 20 May 2010 at 11:38 am

    @Sharkboy

    Hitchens’ article is terrible. His criteria for whether a disorder exists are pretty bad; he doesn’t demonstrate any awareness of construct validity; he makes up alternative hypotheses for ADHD diagnoses and thinks that is meaningful, but hasn’t looked at whether other people are considering and testing for the variables he raises (they are); and he collapses any distinction between knowledge of etiology with knowledge of a disorder.

    He says why does it affect boys so very much more than it affects girls? No other medical complaint – except those involving reproductive organs – discriminates between the sexes in this way but plenty of pathology is sex-linked. I conclude that he doesn’t know what he is talking about. I can’t find a justification for paying Hitchens’ any mind, but maybe someone else can.

  22. colli037on 20 May 2010 at 1:25 pm

    I don’t think natural pesticides or even going all organic will help. 20 years ago there was this

    http://www.pnas.org/content/87/19/7777.full.pdf+html

    discussing the naturally occurring carcinogens produced by plants, many in response to predation.

    if anything, switching to all organic produce only changes the types of carcinogens not the amount.

  23. Calli Arcaleon 20 May 2010 at 3:56 pm

    VRAlbany — thanks!!! I’m going to enjoy looking through those links. And thank you for what you do; you may be “only a tech”, but your work is very important all the same.

  24. the bug guyon 23 May 2010 at 9:25 am

    Malathion 50% is still regularly sold for residential and garden use. The Chlorpyrifos residential label was removed in 2000, but it is certain that unused product was in use during the 2001-2004 period of data collection. For reference, my hazardoous waste program still regularly collects chlorpyrifos products ten years after the label removal. Hell, we still receive a couple of containers of residential DDT a year.

    Malathion is also commonly used for mosquito control, though that has been in decline for the last decade as programs shift to synthetic pyrethroids.

    Therefore, non-food exposures to OPs should be considered in the analysis.

    Calli – the material you mentioned as coming from chrysanthemums is pyrethrum. Pyrethrins and pyrethroids were all developed from that and for the most part, were designed to have lower avian and mammalian toxicity.

    While organic farming uses a lot of excellent techniques that need to be included in conventional farming, the pest control materials allowed really aren’t always safer than those excluded and in some cases, like copper sulfate as a fungicide, is more toxic and more persistant in the environment.

  25. [...] There is a recent study which has garnered a great deal of press linking organophosphates – a type of synthetic pesticide – to higher prevalence of ADHD. However, this is a preliminary observational study. While interesting, it really can only be used to justify further research, not any conclusions regarding the effects of organophosphates. (I discuss this article in more detail here.) [...]

  26. desireeon 26 May 2010 at 7:53 pm

    is it reasonable to think that pesticide exposure at ages 8 to 15 could harm neurological development enough to cause ADHD? i would think that if pesticides were significant, then prenatal or infant/early childhood exposure would be much more important. are we assuming that exposures are the same throughout childhood? isn’t that a pretty big assumption?

  27. twazaon 03 Jun 2010 at 7:22 am

    Thanks for an excellent analysis.

    There were some details in the paper that I either did not understand, or indicate flaws in the authors’ thinking.

    1)
    If adenosine is produced by the body as a natural self-analgesic, why isn’t it produced as a response to the injury in the mouse’s paw?

    2)
    If adenosine and CCPA act locally and diffuse very slowly, how could their manipulations affect the ilias nerve, which was partially ligated (presumably some distance away from the Zusanli point) to create neuropathic pain.

    3)
    Were there control mice that had the incision, but not the nerve ligation? This would separate the effects of pain from the ligated nerve and the effects of pain from the incision.

    4)
    “We next modeled neuropathic pain by spared injury of the sciatic nerve (22)”

    What does “spared mean”?
    The reference 22 seems beside the point as it throws no light on what they are saying.

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