Developmental neurotoxicity of industrial chemicals

Abstract

In asserting the existence of a “silent pandemic” of developmental neurotoxicity, P Grandjean and P J Landrigan (Dec 16, p 2167)1Grandjean P Landrigan P Developmental neurotoxicity of industrial chemicals.Lancet. 2006; 368: 2167-2178Summary Full Text Full Text PDF PubMed Scopus (1442) Google Scholar have apparently forgotten or ignored dose-response principles in their zeal to promote their opinions. In compiling their list of “chemicals known to be neurotoxic in man”, they derive much of their information from occupational exposure studies done when hygiene measures were much less stringent than they are now. Therefore, those results are of limited relevance to assessing general population risks, including those of sensitive populations (pregnant women, infants, children) in whom exposures are much lower.Grandjean and Landrigan's faulty logic is exemplified by ethanol. Abuse during pregnancy causes fetal alcohol syndrome, a developmental syndrome with neurological manifestations. However, there are no data to show that maternal exposure to low, environmentally relevant levels of ethanol (ie, concentration in foods) places the fetus at any risk of fetal alcohol syndrome. Risk is a function of dose, even for developmental neurotoxicity.With drugs, to see efficacy, a critical concentration at the target site is needed. The same principle applies to toxicity. Effects at high doses will not be realised at lower doses if the concentration falls below the target site threshold level. If Grandjean and Landrigan's logic is applied to drugs, an “outbreak of cures” would be predicted to be triggered by any dose of any therapeutic agent. Evidence-based medical practice would reject such a homoeopathic belief. Evidence-based toxicology and epidemiology dictates a similar conclusion with respect to Grandjean and Landrigan's allegations of a “pandemic” of developmental neurotoxicity.I am an independent scientific consultant, and have served as a consultant on toxicology and risk assessment issues to the American Chemistry Council, a trade organisation that represents chemical manufacturers. In asserting the existence of a “silent pandemic” of developmental neurotoxicity, P Grandjean and P J Landrigan (Dec 16, p 2167)1Grandjean P Landrigan P Developmental neurotoxicity of industrial chemicals.Lancet. 2006; 368: 2167-2178Summary Full Text Full Text PDF PubMed Scopus (1442) Google Scholar have apparently forgotten or ignored dose-response principles in their zeal to promote their opinions. In compiling their list of “chemicals known to be neurotoxic in man”, they derive much of their information from occupational exposure studies done when hygiene measures were much less stringent than they are now. Therefore, those results are of limited relevance to assessing general population risks, including those of sensitive populations (pregnant women, infants, children) in whom exposures are much lower. Grandjean and Landrigan's faulty logic is exemplified by ethanol. Abuse during pregnancy causes fetal alcohol syndrome, a developmental syndrome with neurological manifestations. However, there are no data to show that maternal exposure to low, environmentally relevant levels of ethanol (ie, concentration in foods) places the fetus at any risk of fetal alcohol syndrome. Risk is a function of dose, even for developmental neurotoxicity. With drugs, to see efficacy, a critical concentration at the target site is needed. The same principle applies to toxicity. Effects at high doses will not be realised at lower doses if the concentration falls below the target site threshold level. If Grandjean and Landrigan's logic is applied to drugs, an “outbreak of cures” would be predicted to be triggered by any dose of any therapeutic agent. Evidence-based medical practice would reject such a homoeopathic belief. Evidence-based toxicology and epidemiology dictates a similar conclusion with respect to Grandjean and Landrigan's allegations of a “pandemic” of developmental neurotoxicity. I am an independent scientific consultant, and have served as a consultant on toxicology and risk assessment issues to the American Chemistry Council, a trade organisation that represents chemical manufacturers. Developmental neurotoxicity of industrial chemicals – Authors' replyLaura Plunkett seems to have missed a main point of our review—ie, that during prenatal and early postnatal development the timing of exposure is at least as crucial as the dose. It is the unique sensitivity of the developing human brain during windows of early vulnerability that accounts for the profound damage caused by minute doses of lead, methylmercury, ethyl alcohol, and probably many other industrial chemicals that have never been properly tested. As we show with the few chemicals that are known to damage brain development, waiting for the production of detailed dose-response relations will promote the continued exposure of developing brains to toxic risks. Full-Text PDF