Neurodevelopmental toxicity: still more questions than answers – Authors' response
Authors: Philippe Grandjean, Philip J Landrigan
Journal: The Lancet Neurology (2014)

We are grateful for the comments on our review.1Grandjean P Landrigan P.J. Neurobehavioural impact of developmental toxicity.Lancet Neurol. 2014; 13: 330-338Summary Full Text Full Text PDF PubMed Scopus (1270) Google Scholar Our aim was to present a balanced assessment based on our best professional judgement concerning toxicity of industrial chemicals to the developing human brain. The diversity of opinion expressed in these letters reflects the serious absence of neurotoxicity information about most chemicals, but we interpret all four letters as supportive of a call for intensified research. Goldstein and Saltmiras echo Monsanto's oft-repeated defence that glyphosate is a safe herbicide. Still, the toxicity documentation publicly available on this widely used substance is limited. We have been unable to find documentation of any neurotoxicity testing of glyphosate considered valid by the US Environment Protection Agency. Experimental evidence lends support to the likelihood of neurotoxicity.2Cattani D de Liz Oliveira Cavalli VL Heinz Rieg CE et al.Mechanisms underlying the neurotoxicity induced by glyphosate-based herbicide in immature rat hippocampus: Involvement of glutamate excitotoxicity.Toxicology. 2014; 320: 34-45Crossref PubMed Scopus (174) Google Scholar On the basis of clinical reports mentioned by Goldstein and Saltmiras, we therefore believe that glyphosate should be considered a neurotoxic hazard. Monsanto's argument for safety relies on the relative absence of research results rather than on data documenting safety. We agree with Feldman that fluoride is important for children's oral health. However, the fact that a trace element has beneficial effects at low doses in specific tissues does not negate the possibility that neurotoxicity might also be occurring, especially at increased levels of exposure. Indeed, concerns about fluoride toxicity were already raised by a National Research Council expert committee.3National Research Council (NRC)Fluoride in drinking water: a scientific review of EPA's standards. The National Academies Press, Washington, DC2006Google Scholar Feldman describes the recent meta-analysis4Choi AL Sun G Zhang Y Grandjean P Developmental fluoride neurotoxicity: a systematic review and meta-analysis.Environ Health Perspect. 2012; 120: 1362-1368Crossref PubMed Scopus (370) Google Scholar as selective and based on old, confounder-ridden studies. In support of her claims, she refers to two previous reports that reviewed some of the same studies, although without access to important background information. Feldman makes other serious errors—eg, by linking, without justification, a rise in population mean intelligent quotient (IQ) to the introduction of water fluoridation. Similarly, Gelinas and Allukian dispute the validity of previous studies on fluoride exposure and neurobehavioural deficits. We do not deny the importance of a dose-response relation, which has been a unifying concept in toxicology since the time of Paracelsus. However, as we emphasised in our Review, emerging evidence on developmental neurotoxicity makes it clear that the timing of exposure is also of great importance, especially during highly vulnerable windows of brain development. Due to the growing evidence on adverse effects, US authorities now recommend that fluoridation of community water should not exceed 0·7 mg/L.5US Environmental Protection AgencyEPA and HHS Announce New Scientific Assessments and Actions on Fluoride.http://yosemite.epa.gov/opa/admpress.nsf/6427a6b7538955c585257359003f0230/86964af577c37ab285257811005a8417!OpenDocumentGoogle Scholar We agree with Wendroff's perspective, but have been unable to identify epidemiological support for a claim of developmental neurotoxicity from exposure to mercury vapour. As elemental mercury might soon be added to the list of confirmed developmental neurotoxicants, we support the evidence-informed prevention of mercury exposures suggested by Wendroff. In writing our Review, we have tried to steer a middle course between advocates for particular public-health actions and spokespersons for the chemical industry. We believe that sufficient evidence is already available that industrial chemicals endanger human brain development and that unrestrained production and release of such chemicals are short-sighted, dangerous, unsustainable, and fundamentally immoral. We call for a thorough revision of chemical safety policies and for the establishment of a documentation centre on developmental neurotoxicity modelled after the International Agency for Research on Cancer. We declare no competing interests. Neurobehavioural effects of developmental toxicityNeurodevelopmental disabilities, including autism, attention-deficit hyperactivity disorder, dyslexia, and other cognitive impairments, affect millions of children worldwide, and some diagnoses seem to be increasing in frequency. Industrial chemicals that injure the developing brain are among the known causes for this rise in prevalence. In 2006, we did a systematic review and identified five industrial chemicals as developmental neurotoxicants: lead, methylmercury, polychlorinated biphenyls, arsenic, and toluene. Full-Text PDF Neurodevelopmental toxicity: still more questions than answersWe read with interest Grandjean and Landrigan's Review of developmental neurotoxins,1 in which glyphosate herbicide was listed as a human neurotoxicant on the basis of a case report by Malhotra and colleagues.2 The individual in this case report was a 71-year-old man who was unresponsive and in cardiogenic shock with a profound metabolic acidaemia (pH 7·13) and lactic acidosis (7·1 mmol/L; normal levels are 0·5–1·6 mmol/L). He received ventilator support and veno-venous haemodiafiltration and was presumptively managed as having organophosphate intoxication, receiving 239 mg of atropine and 4 g of pralidoxime over an unspecified period of time. Full-Text PDF Neurodevelopmental toxicity: still more questions than answersIn their Review of neurological toxicants,1 Grandjean and Landrigan make unsubstantiated claims and misquote previous studies to pull together heterogeneous elements and drugs into a group of substances termed neurotoxicants. Full-Text PDF Neurodevelopmental toxicity: still more questions than answersIn their Review, Grandjean and Landrigan expressed concern about the neurodevelopmental toxicity of methylmercury,1 but did not assess the dangers of serious and widespread inhalation exposures to elemental mercury vapour (Hg0) from its magico-religious uses in some Caribbean and Latino communities and the presumptive associated latent epidemic of developmental neurotoxicity this constitutes. Full-Text PDF Neurodevelopmental toxicity: still more questions than answersThe American Association for Community Dental Programs' primary goal is to support the efforts of those serving the oral health needs of vulnerable populations at the community level. In view of our commitment to preventing oral diseases and improving access to services for the public, we read with interest Grandjean and Landrigan's Review on neurobehavioral effects of developmental toxicity.1 Full-Text PDF