French Pyrethroid Study Is Full Of Termite Holes

A recent BMJ Occupational and Environmental Medicine paper might be pretty scary looking if you're a parent. Researchers from the Epidemiological Research on Environment, Reproduction and Development, University of Rennes in France maintain that the widely used pyrethroid insecticides are causing behavioral problems in children. But the study is full of holes, which makes the conclusions suspect at best. Here's why.

In order to ascertain the impact of pyrethroids on child neurodevelopment, the group looked for a relationship between the presence of pyrethroid metabolites in urine and certain childhood behaviors. They found one, but what does it really mean?

Between 2002 and 2006, 3,421 pregnant women from Brittany, France were enrolled. When their children turned six, 287 of the mothers filled out a SDQ questionnaire (Strengths and Difficulties Questionnaire), which is designed to evaluate three measures of childhood development—prosocial behavior, internalizing disorders and externalizing disorders. But one doesn't even have to understand what these tests mean or what they measure. This is because the protocol of the study is so flawed that it could be argued that no matter what the result, it won't mean anything.

First, the scares:

"Shelton et al showed that children (aged 2–5 years) of mothers residing near pyrethroid insecticide agricultural applications just prior to conception or during their third trimester were at greater risk for autism spectrum disorders."

"Wagner-Schuman et al found an association among 8- to 15-year-old children between increased urinary levels of the pyrethroid metabolite 3-PBA ... and attention deficit hyperactivity disorder (ADHD)..." 

"Domingues et al showed that levels of 3-PBA were higher in the urine of a group of children (aged 5–12 years) affected by autism spectrum disorders in comparison with those of control children."

Now, the reality:

The fundamental question here is whether the presence of urinary metabolites of pyrethroids can be used to determine anything. This is because pyrethroids are rapidly metabolized and cleared from the body in the urine. Because they don't bioaccumulate, any measurement of urinary metabolites is essentially a snapshot in time of exposure to the chemical in the past few days. This information says nothing about chronic exposure to the pesticides—the only parameter that could account for differences in development over a six-year period. The authors acknowledge this:

"Consequently, pyrethroid metabolites from spot urine samples may not represent a child’s average exposure over time and may result in misclassification, reducing the statistical power to detect associations."

Single measurements of the urinary concentration (pregnant mother and child six years later) cannot be used to draw any conclusions about the effect of pyrethroids on child neurodevelopment. This is analogous to watching one pitch in a baseball game and predicting which team will win.

Urinary metabolites of Permethrin (DCCA and PBA). The red line shows the chemical bond that is broken. The green stars indicate the carbon where oxidative metabolism occurs. 

Other weaknesses include:

• One of the metabolites called trans-DCCA, an isomer of cis-DCCA (1), was found to have the opposite effect of the cis isomer. The chances of this being real are zero. The authors write: "We have no current explanation for the counter-intuitive association observed between childhood high trans-DCCA concentrations and reduced externalizing disorders."  This observation alone is sufficient to cast doubt on the entire study. There is no way that one of the two isomers of permethrin is going to create behavioral disturbances and the other isomer is going to prevent them. None. 
• During the six-year period of development, the children will be exposed to thousands of chemicals, all confounders. For example, lead—a real neurotoxin—was not measured. 
• Questionnaire based data collection is notoriously inaccurate, especially when measuring something subjective, such as child behavior. Recall bias is always an issue with questionnaires. 

The paper goes into great depth about the study, especially focusing on the statistical analysis of the data. But since the initial premise—that urinary metabolites can be used to determine chronic exposure to the chemical—is impossible, all the data and analysis in the world will only serve to take up space. 

Note:

(1) Permethrin is a mixture of cis- and trans- isomers. This is why the cis-DCCA and trans-DCCA metabolites are both detected in urine.