July 16, 2018

expert reaction to study looking at plastic chemicals and rat brains

A new study, published in JNeurosci, reports that adult rats that have been exposed before birth and during nursing to a mixture of chemicals have a smaller prefrontal cortex and perform worse on attention-switching tasks than rats not exposed to the chemicals early in life.

Prof Daniel Nebert, Professor of Environmental Health, University of Cincinnati, said:

“The authors’ abstract states that “Pregnant dams orally consumed an environmentally relevant mixture of phthalates at 0, 200, or 1000 μg/kg/day through pregnancy and for 10 days while lactating”.  From the literature, I see that the no-observed adverse effect level (NOAEL) for reproductive and developmental effects is 4.8 mg/kg body weight per day, and the tolerable daily intake (TDI) for humans is 0.05 mg/kg body weight per day.  Although authors say “an environmentally relevant mixture”, the two doses that they gave to their rats were 4 times and 20 times, respectively, higher than the tolerable daily intake.  Therefore, I find nothing about these findings that might be considered exciting, or unexpected.”

Prof Ieuan Hughes, Emeritus Professor of Paediatrics, University of Cambridge, said:

“This is a well designed study from an experimental perspective using a rodent model to examine yet again the effects of plastics (phthalates) environmental exposure during pregnancy on development of the offspring, in this case cognitive flexibility in adult male and female rats.  These functional studies were coupled with detailed examination of the brain which showed that an area called the medial prefrontal cortex was smaller in size and contained fewer neurons.  How this occurred could not be worked out precisely from this study; the authors were not even certain that it was an endocrine-disrupting effect which has hitherto been the main study of the toxic effects of phthalates.  Indeed, the authors even discuss that phthalates (of which there are several, each acting differently) operate promiscuously on diverse systems such as steroid enzymes, cannabis and nicotine receptors, insulin signalling and function of the thyroid gland.  How can the authors really then suggest the quantum leap that the effects seen in these rat experiments may be relevant to the cause of some neuropsychiatric disorders in humans where the equivalent region of the brain is involved in executive function?”

Prof Alastair Hay, Professor (Emeritus) of Environmental Toxicology, University of Leeds, said:

“This study in rats has been conducted very well indeed.  In contrast to many studies done in the past the authors of this study have selected a mixture of phthalates and doses which are comparable to some higher human intakes.  Their findings that phthalate intake reduces the number of neurons and synapses (connections) in a part of the brain cortex is concerning and requires confirmation by others.

“The phthalates are of concern because of their potential endocrine-disrupting properties.  When these chemicals were first highlighted as a concern the dose tested in animals was way beyond any human exposure.  This new study can not be dismissed for that reason; the doses the authors chose to administer to pregnant rodents and over the first 10 days of lactation are relevant to human intakes.

“The testing regime used to assess learning and performance in the test animals is impressive, exhaustive and robust.

“This study indicates that flexibility of thinking is impaired by the phthalates rather than general learning ability, and this is a first.

“Assessing impacts of exposure to chemicals on the brain is a complex undertaking and eliminating factors which may also influence the findings requires very detailed experimentation and the work described here does all of this very well.  We now need more research to confirm or refute these findings.”

Dr Graham Wheeler, Medical Statistician, UCL, said:

“Due to the small numbers of rats used, the conclusions of these experiments should be treated with some caution.

“Rats that performed the food-finding task were not the same rats that had brain measurements taken.

“As the dose of phthalates increases, we’d expect the rats to make more errors in the food-finding task.  However, rats given the highest dose of phthalates often made fewer errors than those given the lower dose.”

Dr Oliver Jones, Associate Professor of Analytical Chemistry, RMIT University, Melbourne, said:

“This is an interesting study that seems to have been conducted carefully and with considerable thought.  It was particularly nice to see that the authors made a detailed effort to base the doses used in their study on real exposure data (not always the case).

“I think the study itself is very clever, however, while the results might at first sound a bit scary we should keep in mind that results from animal studies don’t always translate to humans (something touched on in this paper) or even to other animals.  For instance, aspirin causes birth defects in mice, but not in humans and cortisone causes birth defects in mice, but not in rats.  We don’t know humans would respond the same way, or even at all, let alone the underlying biochemical mechanisms responsible.  Phthalates are already disappearing from many products in response to consumer pressure, but I think more work is needed before we have the full answer on this topic.”

* ‘Perinatal exposure to an environmentally relevant mixture of phthalates results in a lower number of neurons and synapses in the medial prefrontal cortex and decreased cognitive flexibility in adult male and female rats’ by Daniel G. Kougias et al. published in JNeurosci on Monday 16 July 2018.

Declared interests

Prof Daniel Nebert: “No interests to declare.”

Prof Ieuan Hughes: “No conflicts.”

Dr Graham Wheeler: “I am employed by UCL and have a visiting researcher position at the MRC Biostatistics Unit at the University of Cambridge.  I am a Fellow and a Statistical Ambassador of the Royal Statistical Society, and a voluntary research committee member for Chiltern Music Therapy, a not-for-profit organisation providing music therapy services.  I have no financial conflicts of interest.”

Dr Oliver Jones: “I have no conflicts of interest to declare.  While I have research interests in Phthalates and BPA in food and the environment I don’t have, and have never had, any funding for such work.”

None others received.