EXPERT REACTION: Common plastic chemicals affect rat brain development

In summary, this is a well constructed study that added a minor detail to what we already know about these industrial chemicals. The researchers missed a chance to do something much more significant - compare the impact of a mixture with that of the single components of that mixture.

Background:
A lot is already know about the toxicity of phthalates and our exposure to them. The molecules of these substances are constructed from phthalic acid, and because it has two points of attachment to other chemical groups we get diethyl phthalate, dibutyl phthalate, and so on.  These are sticky liquids that are used as plasticisers, incorporated into plastics to make them softer and more pliable.

In various ways the phthalates leak out of the plastics and end up in the environment where, because they are fat-soluble, they can get into the food chain. Because they have been used for many decades, phthalates can be found everywhere - in scavenger species like ants, in our foods, and in our bodies. Our body burdens are very low but phthalates (along with many other industrial chemicals)  can be detected in our blood and in our urine (as we get rid of them).

As toxins, the phthalates are not in the class of serious poisons like arsenic and novichok. Rather, they exert subtle effects on human development, effects that are small and hard to detect, These effects were often not tested for when the phthalates were introduced for widespread use.

Toxicity testing:
There are three things to note about the testing of chemical substances for health effects:
(i) they are tested one by one;
(ii) they are tested for a suite of effects. From time to time, new effects are noticed and the substances are retested (examples like DDT come easily to mind, as does - in a related field where the same 'foresight' problem arises - the impact of CFCs on the ozone layer). New testing can result in formerly acceptable substances being banned, at least in some applications. This has happened to some phthalates;
(iii) the results of tests with bacteria, water fleas, rats and mice may not translate well to humans. We could be more or less affected than the tests indicate. Where humans are tested, 'we' normally means adult males.

Population studies:
It is not allowed to dose people with suspect substances to see what happens! Much of the evidence relating to humans is obtained with studies of cell cultures or individual tissues, but there are population studies in which the concentration of the suspect chemical substance in blood, urine or other body material is matched with the incidence of various kinds of cancer, immune function or behaviour (mental acuity, for example).

Mixtures:
Questions have been raised over the last few decades about the toxicity of mixtures. There is no guidance on how the results for single chemical substances can be used for considering mixtures. Will the mixture be more potent than the sum of the constituents (synergy), will it be less potent, or just the same? What if the constituents are chemically very similar, and what if they are quite different? Very few studies have been done with mixtures, so these questions are unanswerable.

The present study:
The authors of this paper in the Journal of Neuroscience fed a mixture of phthalates to pregnant rats. Tested when they reached adulthood, the offspring were not as smart and their brains had some unusual features. The same team had used the phthalate mixture to study other functions of pregnant rats, in which they detected modest effects.

In both cases a mixture of six phthalates in proportions 35:21:15:15:8:5 was used. These were the proportions of the six phthalates that the researchers had found in the urine of a group of pregnant women in Illinois. They took the results (quite reasonably) to be typical of the American population. The human urine concentrations were very small, and the rats were exposed to comparably low concentrations. The effects would have to be described as 'modest' rather than 'startling' and they don't add much to the existing pressures against the use of phthalates (some phthalates in some uses).

They missed the point:
I think the authors missed a chance to throw some light on the mixture questions that I outlined above. That would be much more important than uncovering a new effect of phthalates. If they had done experiments with single phthalates, they would have been able to answer the question: does a dose of the mixture produce the same effect as the same dose of a single phthalate?  How about two or three phthalates instead of six?