November 7, 2006

scientists react to Lancet paper on industrial chemicals and brain development

A joint US / Danish report published in the medical journal, The Lancet, has warned of a potential pandemic of juvenile brain disorders brought on by industrial chemicals.

Professor Mark Hanson, Director of Developmental Origins of Health & Disease at Southampton University, said:

“The authors have put their finger on something which is important and which will not go away – namely that in the past we thought of chemical agents such as those listed as potential poisons or overt disruptors of development in a major way. Toxicity testing was done according, e.g. to look for low birth weight, fetal abnormalities etc. However, there is now experimental evidence that low levels of some of these agents can act by altering the action of normal developmental processes – a good example concerns the endocrine disruptor agents (some of which are metabolites of pesticides) which can alter normal epigenetic processes during development. So they don’t produce gross abnormalities, but rather change the way that the baby’s normal control systems work. This will not produce obvious birth defects, but may predispose to later disease – rather as maternal smoking predisposes to the child becoming obese later.

“The jury is out on whether such effects can alter brain development – given the enormous plasticity of the brain one could argue it either way. But there are precedents for developmental influences altering offspring behaviour and learning ability in animals and indeed some epidemiological data for effects on IQ in humans. The review in a way is timely because it will stir up debate and hopefully generate more research in this area. There is no need to panic, but we can’t ignore this possible problem. And of course it’s no accident that the populations in which development and education are challenged in other ways, e.g. low socioeconomic status in poor parts of the developing world, are also the areas in which such pollutants are abundant. One wonders whether the furore over the claim in the press over the weekend that African people are less intelligent, and that this is why they do not make progress, is in fact the wrong way round. Do environmental chemical exposures limit brain development and function under such conditions so they are disadvantaged from early life?”

Professor Alan Boobis, Section of Experimental Medicine and Toxicology at Imperial College London, said:

“The authors of this review have raised an issue of significant concern, but some of the evidence in support of the conclusions lacks rigour. For example, the evidence that fluoride is neurotoxic to developing animals is highly questionable, the levels of alcohol associated with fetal alcohol syndrome are generally higher than the levels of chemicals encountered in the environment, there have been a number of studies on the developmental neurotoxicity of pesticides over the last few years, and these do not support a systematic under-estimation of the sensitivity of the developing fetus compared with other tests in current use. Indeed studies have shown that the developing fetus is not systematically more sensitivity to neurotoxicants than adults, it depends on the compound. In part this is because the developing fetus is potentially vulnerable and as a consequence protective mechanisms have evolved to protect the fetus in utero, at least to some extent.

“On the one hand the authors claim a silent pandemic of neurodevelopmental disorders from industrial chemicals whilst on the other they propose a precautionary approach in which exposure limits for chemicals should be set at values that recognise the unique sensitivity of pregnant women and young children. Hence in essence this is not really a scientific debate but one on the application of the precautionary principle. This is a risk management issue. In implementing the precautionary principle it is important to take into account all relevant information and not just the potential harm that might result from inaction. For example what would the consequence (health, economic, societal) if some of the compounds on the list were banned or severely restricted on the basis of the precautionary principle. This aspect of the debate is absent from the review.

“My own opinion is that current testing strategies, when adequately conducted, are not overlooking developmental neurotoxicants such that pregnant woman and the fetus are being exposed to potentially harmful levels of these chemicals. However, this is a reflection of my own interpretation of the data and I realise that some will interpret the data differently.”

Professor Nigel A Brown, Dean of Faculty of Medicine and Biomedical Sciences, Head of Division of Basic Medical Sciences St George’s, University of London, said:

“This is a campaigning article and should be treated as such. The campaign is worthwhile: the protection of the developing human brain. Who could not support that? However, in their enthusiasm the authors verge on scaremongering. There is nothing new here; no original insights or concepts. It is a review only in the most superficial sense: there are no meta-analyses; no considerations of mechanisms; no calculations of minimal toxic concentrations; no discussion of actual human exposure levels. These are, of course, difficult issues, but that is no excuse for ignoring them.

“One assumption they make is that the developing brain is inherently much more susceptible to chemicals than is the adult brain (citing, in support, a book published almost 40 years ago). This is misleading, at best. The authors accurately mention the very many cellular processes are required for normal brain development and that these do not occur in the adult brain. Clearly then, one can conclude that the developing brain must be differently susceptible to chemicals than the adult brain. There is no logic, however, for assuming that a chemical which is toxic to the adult brain will necessarily be more toxic to development. Obviously, that depends critically on the mechanism of toxicity. There are, indeed, some chemicals for which this is the case, but there are others for which it is not, because their mechanism acts on mature neurons but not on developmental processes.

“From their assertions, the authors conclude that the combined evidence suggests that neurodevelopmental disorders caused by industrial chemicals has created a silent pandemic in modern society. This is a gross over-statement. It is possible that there is a problem, we should be aware of this and we should study the problem, but there is currently not a shred of evidence of a pandemic.

“The authors end by advising physicians to use prudence when counselling patients; wise words indeed, unlike some of those that precedes them here.”