February 17, 2014

expert reaction to industrial chemicals and neurodevelopmental disorders

Research published in Lancet Neurology called for an overhaul of industrial chemical regulations due to a suggested link between such chemicals and neurodevelopmental disorders.

Prof Sir Colin Berry, Emeritus Professor of Pathology, QMUL, said:

“Organic mercury compounds and metallic mercury are known to be neurotoxicants and industrial controls on their use have proved effective in reducing human exposures, as have controls for lead. For PCBs, there is some evidence of changes in humans following poisoning incidents with contaminated oils in cooking, however although widespread exposure at various well-documented levels has been the subject of epidemiological study there is no significant evidence of developmental neurotoxicity in the large populations studied.

“Some of the compounds mentioned in this review are already no longer in use and world-wide levels of contamination have diminished and continue so to do with time.

“In citing new data the authors are quick to dismiss confounding factors without saying why they are able so to do.  There is a willingness to extrapolate from high level exposures where toxicity is evident to the very low level exposures to some of the “new” toxicants that we now see identified by the authors.

“This is a repetition of the bisphenol A sort of argument – just because you can show an effect at a high dose it does not mean that observation is relevant to likely population exposures.  The validity and reproducibility of extrapolation from effects seen in testing at low levels has not been established.

“Some of these compounds have real benefits, for example some are fire retardants, and the often criticised phthalates are necessary to ensure the correct physical properties of disposable catheters etc.”

Prof Tony Dayan, Emeritus Professor of Toxicology, University of London, said:

“The review by Professors Grandjean and Landrigan associates a large number of chemicals in common industrial and even domestic use with possible effects on the development and functioning of the human brain.  There are limitations to this review.

“The review itself is based on a number of previously published epidemiological surveys.  These individual studies are of variable power, meaning we can’t be sure how reliable or large the effects reported in each case are, and some of the studies the authors looked at are meta-analyses and the quality of the work on which they are based is not always clear.  It is difficult to interpret all the individual studies together because there is considerable uncertainty in how to detect and measure the claimed effects of various chemicals on brain development, and because effects may have been measured differently in different individual studies.  Another limitation is that some of the studies on which this review is based were done in animals, and it is dangerous to transfer results from one species to others without a great deal of care and reservations, particularly when considering cognitive and other neurological functions.  So we don’t know whether effects of all of these substances would be the same in humans.

“It is appropriate to control exposure to chemicals at all ages but the demonstrable benefits of the use of many compounds must be taken into account as well as the possibility of harm.  For example, some of these compounds are used as insecticides and have a vital role in preventing malaria and other catastrophic diseases, including typhus and sleeping sickness.  Other chemicals they mention are important in preventing fungal infections of grain and nuts, and others in preserving many medicines and foodstuffs in various storage containers.”

Prof Andy Smith, senior scientist at the MRC Toxicology Unit (in Leicester), said:

“The epidemiological studies that this review looked at have reported links between toxicity of synthetic chemicals and brain development differences.  However, these studies mostly identify associations rather than causal relationships. As usual thousands of chemicals of ‘natural’ source are not considered.

“Like the issue of endocrine disruptors, the implication that present exposure to minute levels of many thousands of synthetic chemicals, even as mixtures, are strong drivers of highly complex neurological disorders and intelligence should be considered with reservation.

“Without sound evidence, a precautionary approach at first appears reasonable, but in the present absence of well validated methodology for developmental toxicity in humans, the implication for pragmatic chemical regulation and substitution and the impact on economic and health output is simplistic.”

Dr Payam Rezaie, Reader in Neuropathology, Brain and Behavioural Sciences, Department of Life, Health and Chemical Sciences, Faculty of Science, The Open University, said:

“There is growing evidence to suggest that prenatal exposure to certain contaminants in the environment such as organophosphates or lead, impacts on brain development and may increase the risk for developing behavioural problems and neurodevelopmental conditions later on in childhood. Avoiding occupational exposure to known teratogens, pesticides or solvents during pregnancy is a recognised measure taken to prevent risk to the unborn child.

“However, further research is required to ascertain whether the developing brain is adversely affected by industrial chemicals in widespread use, and if so, at what levels. Possible environmental causes for neurodevelopmental conditions such as autism and ADHD remain to be established.”

Prof David Coggon, Professor of Occupational and Environmental Medicine, University of Southampton, said:

“I am surprised that Lancet Neurology chose to publish this paper.  There is no attempt to review evidence systematically and critically.  For example, trends in the prevalence of autism spectrum disorder and attention deficit hyperactivity disorder are difficult to determine because of possible changes in diagnostic practice and the completeness with which cases are ascertained.  And discerning small effects of environmental neurotoxicants on outcomes such as IQ is complicated by uncertainties in the quantification of exposures and the potential for confounding by other influences on cognitive development.

“Because the paper lacks rigour, it is impossible to assess the validity of the authors’ claims, many of which seem highly speculative.  The conclusions of more focused and thorough reviews have been less alarming.”

Prof Jean Golding, Emeritus Professor of Paediatric and Perinatal Epidemiology, University of Bristol, said:

“I do agree with the basic tenet that many chemicals are introduced into the environment without being tested for safety, particularly in regard to effects on young children. However it is a pity that the authors have oversold this message with basic scare statements based on inconclusive studies. For example, they quote autism, ADHD, cerebral palsy and dyslexia and imply that these severe disorders are known to be associated with such chemicals – yet there is no definitive evidence of this. They claim that the number of chemicals shown to be associated with harmful effects has doubled from 6 to 12. I looked to see what evidence there was, for example, to implicate high fluoride, which they quote as one of the new chemicals, but they quote only one paper; this only compares the mean IQs of children in villages with different levels of fluoride, with no allowance made for any other differences, and no actual measurement of fluoride in individual children, and comparison with their IQ. This is not good evidence.”

Prof Jon Ayres, Professor of Environmental and Respiratory Medicine, University of Birmingham, said:

“This is an interesting review albeit couched in rather dramatic language.  Some of the arguments are more emotional than quantitative although the underlying concern about developmental neurotoxicity of some chemicals is well founded. A first step would to be to formally quantify these putative effects before embarking on regulatory efforts which may be difficult to put into place. Regulation will need a good indication of the real benefit likely to accrue and that will require a better measure of true impact from proven causal relationships rather than simple associations.”

Prof Charles Newton, Cheryl & Reece Scott Professor of Psychiatry, University of Oxford, said:

“This is a very timely paper. Many of us working in different parts of the world are very concerned about the pervasive effects of certain industrial chemicals on child development. I think the authors are correct in highlighting the potential damage that these chemicals might cause, particularly in countries where the legislation restricting the use of these chemicals does not exist or if it does, is not enforced. For example, the evidence that lead is associated with developmental impairment and reduced IQ is compelling, but leaded petrol is still sold in many parts of Africa despite the United Nations planning to make it obsolete by 2013.

“The relationship between neurotoxins and many neurodevelopmental disorders such as autism is more tenuous. Associations have been reported, but as the authors say, the results are often difficult to interpret. However, the authors raise an important concern; the long-term impact of exposure to these compounds is largely unknown, and it may lead to an increase in the neurodegenerative diseases in the future”.

‘Neurobehavioural effects of developmental toxicity’ by Grandjean & Landrigan published in the Lancet Neurology on Saturday 15 February 2014