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  • Jim Ferraro

Evidence for Developmental Damage

I had placed on the stand at the Castillo-DuPont trial the renowned Dr. Vyvyan Howard, a doctor and researcher who specialized in developmental toxicology and pathology.

Dr. Howard had begun his testimony under my questioning and went on to describe how in rat studies benomyl was found to interfere with the cellular division process by stopping the formation of tubulin, one of the basic proteins in the cells of animals.

Tubulin is needed to form microtubules. These microtubules are required for a number of processes in the cell. When the cell starts to divide, it builds a skeleton along which chromosomes can migrate during division. That skeleton is made of tubulin. Tubulin is also involved in what’s called cell motility—the ability of a cell to move or for movement to occur within cells.

All these capabilities, including cell proliferation, cells being able to move around, and cells being able to grow, are required for the normal development of the nervous system. Interestingly, the process described by Dr. Howard works exactly the same in plants, animals, and humans.

In this particular case, Dr. Howard saw a lot of evidence—in fact, he reviewed over 4,000 pages of documentation in his laboratory, which enabled him to assess the different possible ways exposure occurs. Ingestion (eating), inhalation (breathing), or transdermal or dermal assimilation (through the skin) were the only viable methods in this case.

In addition to Dr. Howard, we had the 12 other experts, including a geneticist, a chemist, a neuro-­ophthalmologist, a developmental toxicologist, an OB/GYN, a fetal pathologist, and more. But Dr. Howard was the most important expert because he was, in essence, the captain of the team.

He did what is known as a “differential diagnosis.” A differential diagnosis is the process by which other possible causes, if any, are ruled out. It’s commonly done throughout medicine and, for that matter, in many other scientific disciplines. Simply put, it is a process of elimination. Here, Dr. Howard’s differential diagnosis covered both the mode of exposure (ingestion, inhalation, or dermal) and the process of ruling out specific environmental causes (e.g., vitamin K, hypothermia, etc.).

How did he do this?

• First, Dr. Howard looked at ingestion. We all have minute traces of various chemicals in our bodies, which get in through our diets. Benomyl is one of those chemicals that can possibly be taken in by eating, but since anything that goes through the stomach also goes through the liver, where it’s detoxified and then excreted by the kidneys, diet was an unlikely consideration in this case, although it could be one port of entry.

• Next Dr. Howard considered inhalation as a means of exposure. At the time, DuPont had released the results of a study it conducted that suggested benomyl could be inhaled from a spray. Dr. Howard made some calculations based on the results of that study as well as those of another study performed in England at DuPont ICI (Imperial Chemical Industries), which sells benomyl or Benlate under license from DuPont. Those calculations convinced Dr. Howard that inhalation was not a likely cause of Donna Castillo’s exposure.

• Finally, Dr. Howard explored dermal transmission through the skin. As it happened, DuPont ICI also did a study that looked at transmission rates through human skin. The ICI study took human skin from fresh female postmortem specimens; put it into a special petri dish, which the researchers painted with a standard solution of benomyl at a known concentration; and then measured how much benomyl transported itself through the skin over the course of twenty-four hours. This study provided a quantitative measure of the amount of Benlate that could actually be transported into the body if the skin was contaminated.

Transdermal absorption was a major consideration in this case. Dr. Howard assessed this as the most likely form of exposure that caused Johnny to be born with no eyes.

Together these diagnoses began to prove beyond a doubt to Dr. Howard that Benlate had caused the blindness in Johnny Castillo.

In my next post, I will continue recounting Dr. Howard’s testimony, and I’ll provide further context for what happened to Donna Castillo when she was exposed to the fungicide.

In the meantime, I’d love to hear from you. How often do you resort to jargon in your work – and do you make an effort to remove such language from your reports, in order to make them clearer to the layperson? Thank you for sharing.


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