1 Grandjean P

Landrigan P.J. Neurobehavioural impact of developmental toxicity. We are grateful for the comments on our review.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.

2 Cattani 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. 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.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.

3 National Research Council (NRC) 4 Choi AL

Sun G

Zhang Y

Grandjean P Developmental fluoride neurotoxicity: a systematic review and meta-analysis. 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.Feldman describes the recent meta-analysisas 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.

5 US Environmental Protection Agency

EPA and HHS Announce New Scientific Assessments and Actions on Fluoride. 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.

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.