Correspondence
ingested in seafood, occupants of such contaminated dwellings cannot control their inhalation exposure and will be unaware of the neurotoxicity of residual mercury in flooring. Mercury sales in The Bronx in New York (USA), where many people of Caribbean origin live, suggest that in 1995 alone,4 between 25 500 and 155 000 homes might have been contaminated with mercury and data from similar Caribbean communities in New Jersey showed that at least 2% of apartments had mercury vapour consistent with its cultural use.5 Environmental health scientists, long aware of the hazards posed by ritualistic mercury use and its probable neurodevelopmental sequelae, have not put into action the “precautionary approach that emphasizes prevention and does not require absolute proof of toxicity” advocated for by the authors.1 Despite Grandjean’s previous observation that in “some ethnic groups, metallic mercury is used for magical purposes that may cause substantial exposure to mercury vapor”,6 these exposures and their neurodevelopmental affects are not routinely assessed. That ritualistic mercury exposure contributes to the “silent pandemic of neurodevelopmental toxicity”1 is suggested by a case of acute magicoreligious mercury poisoning in a 3-year-old Puerto Rican girl, apparently due to ritualistic mercury spills by the previous Dominican occupants of the apartment in which she lived. 2,3 Despite more than two decades of awareness of these ritualistic practices and a variety of research on ritualistic mercury sales, use, and reported environmental and clinical mercury levels, the authors’ observation that recognition of widespread subclinical toxicity often did not occur until decades after the initial evidence of neurotoxicity is exemplified by the failure of government agencies and the environmental medical community to substantively assess these exposures. www.thelancet.com/neurology Vol 13 July 2014
I declare no competing interests.
Arnold P Wendroff mercurywendroff@mindspring.com Mercury Poisoning Project, 544 8th Street, Brooklyn, NY 11215, USA 1
2
3
4
5
6
Grandjean P, Landrigan PJ. Neurobehavioral effects of developmental toxicity. Lancet Neurol 2014; 13: 330–38 Mercer JJ, Bercovitch L, Muglia JJ. Acrodynia and hypertension in a young girl secondary to elemental mercury toxicity acquired in the home. Pediatric Dermatology 2012; 29: 199–201. Brannan EH, S Su, BK Alverson. Elemental mercury poisoning presenting as hypertension in a young child. Pediatric Emergency Care 2012; 28: 812–14. Zayas LH, Ozuah PO. Mercury use in espiritismo: a survey of botanicas. Am J Public Health 1996; 86: 111–12. Garetano G1, Stern AH, Robson M, Gochfeld M. Mercury vapor in residential building common areas in communities where mercury is used for cultural purposes versus a reference community. Sci Total Environ 2008; 397: 131–19. Grandjean P. Mercury. In: Landrigan PJ, Etzel RA (eds). Textbook of children’s environmental health. Oxford: Oxford University Press, 2014. 273–80.
The 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 In their Review, Grandjean and Landrigan claim that fluoride might cause neurodevelopmental harm, a claim based on only one paper,2 of which Grandjean is a coauthor. The study methodology contains several flaws that undermine its credibility and calls into question its applicability to the community water fluoridation programme in the USA. The study2 is a meta-analysis of 27 cross-sectional studies done in poor, rural communities in China, Mongolia, and Iran, countries where the drinking water contains high levels of naturally occurring fluoride. The 27 original studies did not adequately
control for a variety of intervening and confounding variables that could have affected intelligence quotient (IQ) scores, such as parents’ education and socioeconomic status and air and water pollution. It is unfortunate that Grandjean and Landrigan did not mention these limitations. Additionally, they did not clearly state that the reference groups in their article2 use water fluoridated at about the recommended level. Thus, another interpretation of their analysis could be that communities fluoridated at the recommended level have a higher IQ. No credible scientific studies show a relation between fluoride consumption and IQ levels; however, several have shown that fluoride ingested at recommended levels is not harmful. Grandjean and Landrigan did not acknowledge the animal study 3 that showed no evidence of a neurotoxic effect of fluoride, even at levels up to 230 times the recommended concentration; an earlier study showing that fluoride causes no harm to children;4 two formal reviews that delineate weaknesses in the Chinese fluoride and IQ studies;5,6 and the conclusion by one of these sets of investigators6 that biological plausibility for a link between fluoridated water and IQ has not been established. Unfortunately, Grandjean and Landrigan’s Review has been aggressively and improperly used by antifluoridationists to frighten the public about the effects of fluoridation, a well-established public health measure that has been shown to be cost-effective and safe. As a result, the public’s oral health, especially that of the most vulnerable people, is put in jeopardy. As advocates for better oral health and for serving the public’s best interest, we are pleased that The Lancet Neurology is providing a forum for credible experts and organisations to reaffirm the safety and cost-effectiveness of fluoridation—a proven public health measure. 647
Correspondence
A statement from Grandjean and Landrigan clearly stating that their addition of fluoride to their list of neurotoxins does not apply to fluoridation at the recommended levels of 0·7–1·2 ppm would clarify our concerns on the misuse and misinterpretation of their paper. We declare no no competing interests.
*Julianna Gelinas, Myron Allukian Jr [email protected] American Association for Community Dental Programs, Nelson Pavilion, Philadelphia, PA 19134, USA (JG, MA) 1
2
3
4
5
6
Grandjean P, Landrigan PJ. Neurobehavioral effects of developmental toxicity. Lancet Neurol 2014; 13: 330–38. Choi AL, Sun G, Zhang Y, Grandjean P. Developmental fluoride neurotoxicity: a systematic review and meta-analysis. Environ Health Perspect 2012; 120: 1362–68. Whitford GM, Whitford JL, Hobbs SH. Appetitive-based learning in rats: Lack of effect of chronic exposure to fluoride. Neurotoxicol Teratol 2009; 31: 210–15. Shannon FT, Fergusson DM, Horwood LJ. Exposure to fluoridated public water supplies and child health and behaviour. N Z Med J 1986; 99: 416–18. Bazian Ltd. Independent critical appraisal of selected studies reporting an association between fluoride in drinking water and IQ: a report for South Central Strategic Health Authority. London, UK. http://www. fairbanksalaska.us/wp-content/ uploads/2011/07/20090211Bazian-ReviewIQ-Studies.pdf (accessed March 18, 2014). European Union Scientific Committee on Health and Environmental Risks (SCHER). Opinion on critical review of any new evidence on the hazard profile, health effects, and human exposure to fluoride and the fluoridating agents of drinking water. May 16, 2011. http://ec.europa.eu/health/scientific_ committees/environmental_risks/docs/ scher_o_122.pdf (accessed March 18, 2014).
Authors’ response We are grateful for the comments on our review.1 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 648
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.2 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.3 Feldman describes the recent meta-analysis4 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 doseresponse 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.5 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.
*Philippe Grandjean, Philip J Landrigan [email protected] Department of Environmental Medicine, University of Southern Denmark, Odense, Denmark, and Department of Environmental Health, Harvard School of Public Health, Boston, MA 02215, USA (PG); and Department of Preventive Medicine, Mount Sinai School of Medicine, New York, NY; USA (PJL) 1
2
3
Grandjean P, Landrigan, P.J. Neurobehavioural impact of developmental toxicity. Lancet Neurol 2014; 13: 330–38. Cattani D, de Liz Oliveira Cavalli VL, Heinz Rieg CE, et al. Mechanisms underlying the neurotoxicity induced by glyphosatebased herbicide in immature rat hippocampus: Involvement of glutamate excitotoxicity. Toxicology 2014; 320: 34–45. National Research Council (NRC). Fluoride in drinking water: a scientific review of EPA’s standards. Washington, DC: The National Academies Press, 2006.
www.thelancet.com/neurology Vol 13 July 2014
ingested in seafood, occupants of such contaminated dwellings cannot control their inhalation exposure and will be unaware of the neurotoxicity of residual mercury in flooring. Mercury sales in The Bronx in New York (USA), where many people of Caribbean origin live, suggest that in 1995 alone,4 between 25 500 and 155 000 homes might have been contaminated with mercury and data from similar Caribbean communities in New Jersey showed that at least 2% of apartments had mercury vapour consistent with its cultural use.5 Environmental health scientists, long aware of the hazards posed by ritualistic mercury use and its probable neurodevelopmental sequelae, have not put into action the “precautionary approach that emphasizes prevention and does not require absolute proof of toxicity” advocated for by the authors.1 Despite Grandjean’s previous observation that in “some ethnic groups, metallic mercury is used for magical purposes that may cause substantial exposure to mercury vapor”,6 these exposures and their neurodevelopmental affects are not routinely assessed. That ritualistic mercury exposure contributes to the “silent pandemic of neurodevelopmental toxicity”1 is suggested by a case of acute magicoreligious mercury poisoning in a 3-year-old Puerto Rican girl, apparently due to ritualistic mercury spills by the previous Dominican occupants of the apartment in which she lived. 2,3 Despite more than two decades of awareness of these ritualistic practices and a variety of research on ritualistic mercury sales, use, and reported environmental and clinical mercury levels, the authors’ observation that recognition of widespread subclinical toxicity often did not occur until decades after the initial evidence of neurotoxicity is exemplified by the failure of government agencies and the environmental medical community to substantively assess these exposures. www.thelancet.com/neurology Vol 13 July 2014
I declare no competing interests.
Arnold P Wendroff mercurywendroff@mindspring.com Mercury Poisoning Project, 544 8th Street, Brooklyn, NY 11215, USA 1
2
3
4
5
6
Grandjean P, Landrigan PJ. Neurobehavioral effects of developmental toxicity. Lancet Neurol 2014; 13: 330–38 Mercer JJ, Bercovitch L, Muglia JJ. Acrodynia and hypertension in a young girl secondary to elemental mercury toxicity acquired in the home. Pediatric Dermatology 2012; 29: 199–201. Brannan EH, S Su, BK Alverson. Elemental mercury poisoning presenting as hypertension in a young child. Pediatric Emergency Care 2012; 28: 812–14. Zayas LH, Ozuah PO. Mercury use in espiritismo: a survey of botanicas. Am J Public Health 1996; 86: 111–12. Garetano G1, Stern AH, Robson M, Gochfeld M. Mercury vapor in residential building common areas in communities where mercury is used for cultural purposes versus a reference community. Sci Total Environ 2008; 397: 131–19. Grandjean P. Mercury. In: Landrigan PJ, Etzel RA (eds). Textbook of children’s environmental health. Oxford: Oxford University Press, 2014. 273–80.
The 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 In their Review, Grandjean and Landrigan claim that fluoride might cause neurodevelopmental harm, a claim based on only one paper,2 of which Grandjean is a coauthor. The study methodology contains several flaws that undermine its credibility and calls into question its applicability to the community water fluoridation programme in the USA. The study2 is a meta-analysis of 27 cross-sectional studies done in poor, rural communities in China, Mongolia, and Iran, countries where the drinking water contains high levels of naturally occurring fluoride. The 27 original studies did not adequately
control for a variety of intervening and confounding variables that could have affected intelligence quotient (IQ) scores, such as parents’ education and socioeconomic status and air and water pollution. It is unfortunate that Grandjean and Landrigan did not mention these limitations. Additionally, they did not clearly state that the reference groups in their article2 use water fluoridated at about the recommended level. Thus, another interpretation of their analysis could be that communities fluoridated at the recommended level have a higher IQ. No credible scientific studies show a relation between fluoride consumption and IQ levels; however, several have shown that fluoride ingested at recommended levels is not harmful. Grandjean and Landrigan did not acknowledge the animal study 3 that showed no evidence of a neurotoxic effect of fluoride, even at levels up to 230 times the recommended concentration; an earlier study showing that fluoride causes no harm to children;4 two formal reviews that delineate weaknesses in the Chinese fluoride and IQ studies;5,6 and the conclusion by one of these sets of investigators6 that biological plausibility for a link between fluoridated water and IQ has not been established. Unfortunately, Grandjean and Landrigan’s Review has been aggressively and improperly used by antifluoridationists to frighten the public about the effects of fluoridation, a well-established public health measure that has been shown to be cost-effective and safe. As a result, the public’s oral health, especially that of the most vulnerable people, is put in jeopardy. As advocates for better oral health and for serving the public’s best interest, we are pleased that The Lancet Neurology is providing a forum for credible experts and organisations to reaffirm the safety and cost-effectiveness of fluoridation—a proven public health measure. 647
Correspondence
A statement from Grandjean and Landrigan clearly stating that their addition of fluoride to their list of neurotoxins does not apply to fluoridation at the recommended levels of 0·7–1·2 ppm would clarify our concerns on the misuse and misinterpretation of their paper. We declare no no competing interests.
*Julianna Gelinas, Myron Allukian Jr [email protected] American Association for Community Dental Programs, Nelson Pavilion, Philadelphia, PA 19134, USA (JG, MA) 1
2
3
4
5
6
Grandjean P, Landrigan PJ. Neurobehavioral effects of developmental toxicity. Lancet Neurol 2014; 13: 330–38. Choi AL, Sun G, Zhang Y, Grandjean P. Developmental fluoride neurotoxicity: a systematic review and meta-analysis. Environ Health Perspect 2012; 120: 1362–68. Whitford GM, Whitford JL, Hobbs SH. Appetitive-based learning in rats: Lack of effect of chronic exposure to fluoride. Neurotoxicol Teratol 2009; 31: 210–15. Shannon FT, Fergusson DM, Horwood LJ. Exposure to fluoridated public water supplies and child health and behaviour. N Z Med J 1986; 99: 416–18. Bazian Ltd. Independent critical appraisal of selected studies reporting an association between fluoride in drinking water and IQ: a report for South Central Strategic Health Authority. London, UK. http://www. fairbanksalaska.us/wp-content/ uploads/2011/07/20090211Bazian-ReviewIQ-Studies.pdf (accessed March 18, 2014). European Union Scientific Committee on Health and Environmental Risks (SCHER). Opinion on critical review of any new evidence on the hazard profile, health effects, and human exposure to fluoride and the fluoridating agents of drinking water. May 16, 2011. http://ec.europa.eu/health/scientific_ committees/environmental_risks/docs/ scher_o_122.pdf (accessed March 18, 2014).
Authors’ response We are grateful for the comments on our review.1 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 648
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.2 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.3 Feldman describes the recent meta-analysis4 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 doseresponse 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.5 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.
*Philippe Grandjean, Philip J Landrigan [email protected] Department of Environmental Medicine, University of Southern Denmark, Odense, Denmark, and Department of Environmental Health, Harvard School of Public Health, Boston, MA 02215, USA (PG); and Department of Preventive Medicine, Mount Sinai School of Medicine, New York, NY; USA (PJL) 1
2
3
Grandjean P, Landrigan, P.J. Neurobehavioural impact of developmental toxicity. Lancet Neurol 2014; 13: 330–38. Cattani D, de Liz Oliveira Cavalli VL, Heinz Rieg CE, et al. Mechanisms underlying the neurotoxicity induced by glyphosatebased herbicide in immature rat hippocampus: Involvement of glutamate excitotoxicity. Toxicology 2014; 320: 34–45. National Research Council (NRC). Fluoride in drinking water: a scientific review of EPA’s standards. Washington, DC: The National Academies Press, 2006.
www.thelancet.com/neurology Vol 13 July 2014
