Bulletin #709

November 13, 2006

Dear All,

I am sure that many of you have seen press accounts of the important paper which was published last week in The Lancet, the premium medical journal in the UK. The article dealt with the impact of chemicals on fetal, infant and child brain development. Some press reports included a reference to the short section on fluoride (The Times of London) and others did not (AP, Nov 10, 2006). This article is so important in my view, that I have copied out the bulk of it below. Even in this shortened version it is long, but it is well worth the time to read through this carefully. I have printed the AP article after the Lancet article.

This article is extremely important on several fronts, including our battles against both water fluoridation and the use of sulfuryl fluoride as a fumigant on food in warehouses.

The authors, Philippe Grandjean & Philip Landrigan, have stuck their necks out and discussed the large universe of chemicals which may impact the developing brain, not just one or two specific chemicals.  The main point of their review is that of the thousands of potentially neurotoxic chemicals for kids, only a very small percentage have been tested in animals, and an even smaller percentage have been investigated in humans.  

Human studies have usually started with high level occupational or accidental exposures among  adults.  Thereupon people have wondered whether lower levels might also affect children.  Of the known developmental neurotoxins (DNT), all of them have been established very gradually, starting first with animal studies, or studies on adult humans, and then – finally - children. Thus, proving a chemical can damage a child’s developing brain in this way can take many years (e.g lead) and in the intervening years, may lead to millions of children being unnecessarily exposed. The authors suggest there is the potential for many more DNTs and point out that the vast majority of chemicals have not even been examined at the first level: animal tests.

This background makes The Lancet review’s discussion of fluoride even more important, because the authors single it out as one of the few which has been examined minimally (in both animals and humans) with the studies thus far indicating it has neurotoxic effects.

Their analogies to the “headliners” of lead, mercury, PCBs (dioxins), and arsenic are also worth discussing.  Basically, the authors are suggesting that fluoride may be next in line (they describe it as an “emerging neurotoxic substance”), but since it took so long to “prove” that lead was a developmental neurotoxin, it may also take a while to “prove” fluoride is as well.

(On a personal note I remember saying in a TV interview I gave on British TV in 1996 that I felt that fluoride, as far as brain damage was concerned, was where lead was in the 1970s.)

The bottom line is that Grandjean and Landrigan are invoking the “precautionary principle”, but not just in a philosophical sense, but using hard evidence to show how our history of determining DNT suggests there is a very real possibility that chemicals like fluoride will be proven to cause DNT.  To ignore and not act on this possibility is totally irresponsible.  And by act, I mean either reduce exposure or immediately invest in high quality studies to determine whether it does or not. Right now in the US this is not being done. In fact, the very opposite is true. When Mullenix found a problem she was fired! What studies we have, therefore, come largely from overseas, particularly China.

In other fluoridating countries, such as Australia, Ireland, New Zealand, no serious fluoride research is being carried out on the brain or any other tissue except the teeth. In the UK, the MRC in 2002 recommended a higher priority for fluoride research on dental fluorosis than on its impacts on the brain! The MRC even dismissed the need to pursue fluoride’s impacts on the pineal gland, even though this research was carried out right under their noses by British researcher Jennifer Luke (1997, 2001).

While we were pleased to see The Lancet’s review refer to a few of the studies on fluoride and the brain, they only viewed the tip of the iceberg. We have repeatedly drawn attention to the fact that over 30 animal studies indicate that fluoride can cause brain damage (and some at very low levels, e.g. Varner 1998), as well as the several studies from China which indicate that naturally occurring fluoride lowers IQ at relatively low levels (1.8 ppm, Xiang, 2003) and at even lower levels if the child has an iodine deficiency (0.9 ppm, Lin Fa-Fu 1991). Research from China has also found that elevated fluoride exposure among pregnant mothers damages the brain of the fetus (Du 1992). Most of these studies were reviewed by the recent NAS panel (NRC, 2006).

Unfortunately, The Lancet review draws attention to only four studies (Mullenix  et al., 1995; Xiang et al., 2003; Lu et al, 2000 and Qin et al.,1990) and leaves the impression that these effects only occur at high fluoride levels. But at least they have broken the ice. The mainstream medical journals hardly mention the issue at all.

This review of the potential for fluoride to interfere with fetal and infant brain development (limited as it was) brings us back, with an increased urgency, to the last bulletin which dealt with the ADA’s advice (very slow in coming) that infants should not be given formula made up with fluoridated tap water. See: http://www.fluoridealert.org/health/infant/

The ADA’s major concern is the dramatic increase in the occurrence of dental fluorosis among American children. With 32% of children now impacted — a 9% increase from the rate in the 1980s (CDC, 2005) — this is hard for even the most pro-fluoridation diehard to deny. But as fluoridation critics have pointed out many times, dental fluorosis is only the first VISIBLE sign of fluoride’s toxic effect on the body. We have to worry about what other less visible and subtle systemic (and largely unstudied) effects may also be occurring commensurate with damage to the growing tooth cells. The NRC (2006) report reviewed the evidence that fluoride may have direct impacts on the brain (there are many possible mechanisms, reviewed as long ago as 1994 by Bruce Spittle), and indirect effects through both lowering of thyroid function (exacerbated by iodine deficiency) and accumulation in the pineal gland (Luke, 1997, 2001).

The ADA’s statement on advising parents not to use fluoridated tap water for infant formula was largely ignored by the media. Now that The Lancet has made visible the potential for fluoride to impact the developing brain, this gives even greater reason for the ADA advice to be recognized and heeded. After all, isn’t the baby’s developing brain more important than its developing teeth?

Thus, inadvertently the ADA, and the FDA (which has recently ruled that claims of fluoridated water’s benefits can not be targeted to infants), and the Lancet review, have provided fresh impetus for halting water fluoridation IMMEDIATELY.  Why? Because even if the ADA and others tried very hard – and there is no indication that they will - their recommendation that infants should not drink fluoridated water will not reach millions of American parents who will continue to use tap water to make up formula, oblivious to its real and potential dangers. It would make far more sense and be far more effective to abandon this shortsighted policy than to embark on an educational campaign to reach the whole population of nursing mothers. It is one thing if this contributes to dental fluorosis, it is quite another if it leads to further brain development problems (subtle as they may be) in our children. Unlike the accidental and localized exposure that some children have to industrial chemicals, millions of children get deliberately and unnecessarily exposed to this chemical every day in their drinking water. As Grandjean and Landrigan make clear for lead, a slight shift in IQ for a whole population has a devastating effect on the number of children with very high and very low IQs, with untold costs to society at large. Urgent action is of paramount importance.

Again, Nature said it first. The level in mothers milk is 250 times lower than that added to water (0.004 ppm versus 1 ppm). It is time to acknowledge that Nature may know a great deal more about what the baby needs - and what may be dangerous for the baby’s brain - than the zealots who continue to promote this practice at the ADA, and the CDC (as well as those who are neglecting their duty on this matter at the FDA). If ever an entity gave a sound foundation for exercising the precautionary principle it must be the guidebook that nature provided in baby’s first meal. A meal consumed at a time when, as Grandjean and Landrigan clearly illustrate in the Lancet article, the developing brain is most vulnerable to neurotoxins.

Paul Connett

###

The Developmental neurotoxicity of industrial chemicals

P Grandjean, PJ Landrigan

Neurodevelopmental disorders such as autism, attention deficit disorder, mental retardation, and cerebral palsy are  common, costly, and can cause lifelong disability. Their causes are mostly unknown. A few industrial chemicals (eg,  lead,  methylmercury,  polychlorinated  biphenyls  [PCBs],  arsenic,  and  toluene)  are  recognised  causes  of  neurodevelopmental disorders and subclinical brain dysfunction. Exposure to these chemicals during early fetal development  can cause brain injury at doses much lower than those affecting adult brain function. Recognition of these risks has  led to evidence-based programmes of prevention, such as elimination of lead additives in petrol. Although these  prevention campaigns are highly successful, most were initiated only after substantial delays. Another 200 chemicals  are known to cause clinical neurotoxic effects in adults. Despite an absence of systematic testing, many additional  chemicals have been shown to be neurotoxic in laboratory models. The toxic effects of such chemicals in the developing  human brain are not known and they are not regulated to protect children. The two main impediments to prevention  of  neurodevelopmental  deficits  of  chemical  origin  are  the  great  gaps  in  testing  chemicals  for  developmental  neurotoxicity and the high level of proof required for regulation. New, precautionary approaches that recognise the  unique vulnerability of the developing brain are needed for testing and control of chemicals.

One in every six children has a developmental disability  and in most cases these disabilities affect the nervous  system. 1 The most common neurodevelopmental disorders include learning disabilities, sensory deficits, developmental  delays, and cerebral palsy. 1 Some experts have reported that  the prevalence of certain neurodevelopmental disorders— autism and attention deficit and hyperactivity disorder, in  particular—might be increasing, but there are few data to sustain  that position. 2  Treatment of  these  disorders is difficult, and the disabilities they cause can be permanent; 3  they are therefore very costly to families and to society. 4–6  

Evidence has been accumulating over several decades  that industrial chemicals can cause neurodevelopmental  damage  and  that  subclinical  stages  of  these  disorders  might  be  common.  The  possibility  of  a  link  between  chemicals and widespread neurobehavioural changes was  first raised by research showing that lead was toxic to the  developing brain across a wide range of exposures. 7–10 That  report was in accord with reports indicating that other  environmental pollutants were also toxic to early brain  development. 11 An expert committee from the US National  Research Council concluded that 3% of developmental  disabilities are the direct result of environmental exposure  to such substances, and that another 25% arise through  interactions between environmental factors and individual genetic  susceptibility. 3  These  estimates were based on scarce information about neurotoxicity and could therefore underestimate the true prevalence of chemically-induced  abnormalities.

Neurobehavioural damage caused by industrial chemicals is, in theory, preventable.  An essential  prerequisite to prevention is recognition of a chemical’s  ability to harm the developing brain. Knowledge that a chemical is neurotoxic can prompt efforts to restrict its use and to control  exposure.  Previous evidence-based programmes of exposure  prevention, such as those directed against children’s exposure to lead, have been highly successful, although they were initiated after  substantial delay.

The aims of this review are to characterise the vulnerability of the developing nervous system to  chemical  toxicity; to collate publicly available data for human neurotoxicity of industrial chemicals;  to examine the possible extent of a developmental neurotoxicity pandemic; to describe the known consequences of developmental neurotoxicity for individuals and society; to examine the implications for human health of the dearth of toxicological information; and to consider prospects  for prevention of exposure.

Vulnerability of the developing brain

The developing human brain is inherently much more susceptible to injury caused by toxic agents than is the brain of an adult. 12 This susceptibility stems from the fact that during the 9 months of  prenatal life, the human brain must develop from a strip of cells along the dorsal ectoderm of the fetus into a complex organ consisting of billions of precisely located, highly interconnected, and specialised cells. Optimum brain development requires that neurons move along precise pathways from their points of origin to their assigned locations, that they establish connections with other cells, both nearby and distant, and that they learn to communicate with other cells via such connections. 12–14  All these processes have to take place within a tightly controlled time frame, in  which each developmental stage has to be reached on schedule and in the correct  sequence.  Because of the extraordinary complexity of human brain development, windows of unique  susceptibility to toxic interference arise that have no counterpart in the mature brain, or in any other organ. If a developmental process in the brain is halted or inhibited, there is little potential for later repair, and the consequences can therefore be permanent. 12,14

During fetal development, the placenta offers some protection against unwanted chemical exposures, but it is  not an effective barrier against environmental pollutants. 15  For example, many metals easily cross the placenta, and the mercury concentration in umbilical cord blood can be  substantially higher than in maternal  blood. 16  The  blood-brain barrier, which protects the adult brain from many toxic chemicals, is not completely formed until about  6 months after birth. 17  

The human brain continues to develop postnatally, and the period of heightened vulnerability therefore extends over many  months, through infancy and into early childhood. Although most neurons have been formed by the time of birth, growth of glial cells and myelinisation of axons continues for several years. 13,14

The susceptibility of infants and children to industrial  chemicals is further enhanced  by  their  increased exposures, augmented absorption rates, and diminished ability to detoxify many exogenous compounds, relative to  that of adults. 18,19  Persistent lipophilic substances, including specific pesticides and halogenated industrial  compounds, such as PCBs, accumulate in maternal  adipose tissue and are passed on to the infant via breast milk, resulting in infant exposure that  exceeds the mother’s own exposure by 100-fold on the basis of bodyweight. 20

 Recognition of neurotoxicity

 Developmental neurotoxicity in children exposed to industrial chemicals is often first identified  through recognition of obvious functional abnormalities after high-dose exposure that clearly caused poisoning. Good  quality research later documented the presence of less striking, but nonetheless serious adverse effects at low doses of exposure (figure 1). This sequence of discovery led to the  recognition that environmental pollutants exert a range of adverse effects—some are clinically  evident, but others can be discerned only through special testing and are not evident on standard  examination, hence the term subclinical toxicity. The underlying idea is that there is a dose-dependent continuum of toxic effects, in which clinically obvious effects have subclinical counterparts. 21 A pandemic of subclinical neurotoxicity is therefore likely to be silent—ie, not apparent from standard health statistics. The notion of subclinical toxicity originates from the  pioneering work of Landrigan 7 Needleman 8 and their colleagues, which, showed that children’s exposure to lead could cause reductions in intelligence and changes in behaviour even in the absence of clinically visible symptoms of lead toxicity. The subclinical toxicity of lead in children has subsequently been confirmed in  prospective epidemiological studies. 22,23  

Parallel findings have been reported on some other  industrial chemicals, but their number is small. About 80,000 chemicals are registered for commercial use with the US Environmental Protection  Agency, and 62 000 were already in use when the Toxic Substances  Control Act was enacted in the  USA in 1977. 24  The situation is similar in the EU, where 100,000 chemicals were registered in 1981. 25 The full extent to which these chemicals contribute to neurodevelopmental disorders and subclinical neurotoxicity is still unknown.

Neurotoxic agents

Identification  

Studies in animals support the notion that a wide range  of industrial chemicals can cause developmental neurotoxicity at low doses that are not harmful to mature organisms. 26,27 Such injury seems to result in permanent changes in brain function that might become detectable  only when the animal reaches maturity. Because developmental neurotoxicity might not be apparent from routine toxicology tests, 28 identification of neurotoxic chemicals often rests on clinical and epidemiological data.

To identify environmental chemicals that are toxic to  the human brain, we searched the hazardous substances data bank of the US National Library of Medicine, where  substances are listed with their adverse effects in human  beings. We checked the completeness of this list against  other data sources and with a previous review of published  data for clinical toxicity. 29 The panel shows the industrial chemicals known to be neurotoxic in human beings. We have excluded drugs, food additives, microbial toxins, and snake venoms and similar biogenic substances. This  list excludes chemicals that have proved neurotoxic solely  in laboratory animals, for which no systematic list exists.  We mainly include acutely toxic substances that have caused serious accidents or have been used in suicide attempts, Neurotoxins that mainly cause chronic or delayed disease are likely to be underrepresented. 29 The largest groups of identified compounds are metals, solvents, and pesticides, but other chemicals with less  documentation could have unrecognised effects. The list therefore should not be regarded as comprehensive.  These  substance names (see  panel) were used for searches of published data for developmental  neurotoxicity. On the basis of our critical review, the few known chemicals causing neurodevelopmental abnormalities are highlighted in the panel. Many more chemicals that we have not listed are known to harm neurodevelopment in laboratory animals, 27 but no data about their potential toxic effects on human brain development are available.

(There follow sections on Lead, Methylmercury, Arsenic, Polychlorinated biphenyls, Solvents and Pesticides)

 
Emerging neurotoxic substances

Documentation  of  developmental  effects  in  human  beings for the other compounds listed in the panel is poor.  However, three obvious  candidate substances deserve particular attention, including two that have not seemed to cause neurotoxicity in adults.  

Fluoride  

Fluoride can cause neurotoxicity in laboratory animals, 89 but is not shown in the panel as a substance proven to be neurotoxic in man. It exists in drinking water as a natural contaminant, but the concentration is dependent on local geological circumstances.  In rural communities  in China, high fluoride concentrations in well water might cause skeletal abnormalities. In one such community, 222 children aged 8–13 years showed significantly worse IQs than 290 unexposed controls. 90 Parallel results were obtained in a smaller study of 118 children of similar  age. 91 Another study of 477 schoolchildren from 22 villages suggested that both increased water fluoride concentrations and very low concentrations were associated with IQ deficits, compared with children exposed to normal concentrations (below 1  mg/L). 92  The reports  did not thoroughly consider possible confounders, but do suggest that further in-depth studies be undertaken.  

Effects of developmental neurotoxicity

The five substances recognised as causes of developmental neurotoxicity show similar patterns in the development  of scientific documentation of their risks. This pattern of  discovery started in each instance with recognition of  adult neurotoxicity, typically in people with occupational  exposure, and of episodes of acute, high-dose poisoning in children.  The  next stage was the  accumulation of epidemiological evidence of neurobehavioural deficits in children with prenatal exposures at concentrations that are not toxic to adults (figure 1). For lead, methylmercury,  and PCBs, widespread subclinical neurotoxicity has been  documented internationally, yet the full implications of  exposure to arsenic and toluene are unclear. For most substances listed in the panel, only neurotoxicity in adults has been documented.

The combined evidence suggests that neurodevelopmental disorders caused by industrial chemicals has created a silent pandemic in modern society. Although these chemicals might have caused impaired brain development in millions of children worldwide, the profound effects of such a pandemic are not apparent from available health statistics. Additionally, as shown by this Review, only a few chemical causes have been recognised so the full effects of our industrial activities could be substantially greater than recognised at present.

As is shown by the evidence for inorganic lead, globally  increased exposures have been responsible for erosion of  cognitive skills with subclinical, but permanent, decreases  in IQ. Additionally, this neurotoxic chemical produces  lifelong changes in behaviour with shortened attention  span, increased impulsivity, heightened aggressiveness,  slowed motor coordination, and impaired memory and  language  skills.  The  consequences  are  increased  likelihood  of  school  failure,  diminished  economic  productivity, and possibly increased risk of antisocial and  criminal behaviour. 94 The most striking of these effects  occur at the extremes of performance;  in highly exposed  children,  almost  none  had  above  average  function,  whereas  the  number  with  obvious  deficits  increased  greatly. 95  The  most  severely  affected  individuals  will  probably need special education and will also be less  likely  than  their  peers  to  pursue  productive  career  options. A study of adults who were exposed to excess  lead  as  children  revealed  that  they  were  much  less  successful  in  life  than  those  from  a  less  exposed  comparison group. 96

The  consequences  of  a  pandemic  of  developmental  neurotoxicity extend beyond descriptive data for incidence  and  prevalence  of  clinically  diagnosed  disorders. 1,3  Increased risk of Parkinson’s disease 97 or other neurodegenerative diseases 98 is a further potential consequence  of the pandemic. Thus, early subclinical chemical injury  has been postulated to silently kill a fraction of the cells  needed to sustain brain function in later life (eg, in the  substantia nigra). These latent impairments cause no  symptoms in childhood, but could be unmasked during  the natural neuronal attrition associated with ageing. 99,100

The wide extent of human exposure to pollutants is  now becoming apparent after systematic collection of  data for the amounts of these substances present in the  environment and in human tissues. 101 However, recognition of causal associations could be difficult because  exposures vary with time, more than one substance could  have an effect, individual vulnerability varies, and other  factors can bias epidemiological studies toward the null  hypothesis,  especially  when  the  outcome  might  be  unrecognised for several years, or even decades. 102  

The population at risk of subclinical neurotoxicity from  industrial chemicals is very large. Almost all children  born in industrialised countries between 1960 and 1980  were exposed to substantial amounts of lead from petrol  that could have reduced the number of children with far  above average intelligence (IQ scores above 130 points)  by  over  50%  and  might  likewise  have  increased  the  number with IQ scores below 70. 95 In the USA alone, the  aggregate population of children at risk of exposure to  airborne lead at that time was about 100 million. In this  period, the resulting economic costs are estimated to  have ranged from US$110 billion to $319 billion in each  year’s birth cohort. 103 Most of these costs were related to  the diminished economic productivity that resulted over  the exposed children’s entire lifetimes from wide-scale  reductions  in  intelligence.  Today  the  costs  of  lead  poisoning are estimated to be $43 billion in each birth  cohort in the USA, 5 whereas the costs of prenatal methylmercury toxicity are estimated to amount to $8·7 billion  yearly (range, $2·2–43·8 billion). 6 Diminished economic  productivity  remains  the  main  source  of  these  costs.  Because of the absence of dose-response associations for  other  neurotoxic  compounds,  the  total  costs  are  unknown.

The effect of chemical neurotoxicity extends beyond  the industrially developed nations. Toxic chemicals, such  as  highly  dangerous  pesticides  that  are  banned  in  industrialised  countries,  are  exported  to  developing  societies, where environmental and occupational standards are often weak or at least poorly enforced. 104 The  consequences are largely unreported.

Prevention

A  pandemic  of  neurodevelopmental  toxicity  caused  by  industrial chemicals is, in theory, preventable. Testing of  new chemicals before allowing them to be marketed is a  highly efficient means to prevent toxicity, but has been  required  only  in  recent  years.  Of  the  thousands  of  chemicals used in commerce, fewer than half have been  subjected  to  even  token  laboratory  testing  for  toxicity  testing. 24 Nearly 3000 of these substances are produced in  quantities of almost 500 000 kg every year, but for nearly half these high-volume chemicals no basic toxicity data are  publicly available, and 80% have no information about  developmental  or  paediatric  toxicity. 24  Although  new  chemicals must be tested more thoroughly, access to these  data can be restricted, because they could be claimed to  constitute confidential business information. Absence of  information  about  the  neurotoxic  potential  of  most  industrial chemicals is therefore the main impediment to  prevention  of  developmental  disorders  induced  by  neurotoxic  pollutants.  Accelerated  testing  of  chemicals  already in commerce is therefore essential. In the USA, a  legal mandate to require testing was established in the  Toxic Substances Control Act, but is largely unenforced. 24  In the EU, opportunity exists to require more extensive  chemical  testing  through  the  REACH  programme, 25  although  the  proposed  legislation  does  not  emphasise  testing  for  developmental  neurotoxicity  as  a  primary  objective.

 Toxicity  testing  protocols  for  chemicals  need  to  be  expanded  to  include  examination  of  neurobehavioural  functions.  Present  test  protocols  rely  mainly  on  crude  indices, such as brain weight and gross morphology. 105,106  There is a risk that abbreviated protocols used for toxicity  screening will overlook neurodevelopmental toxicity, and  further testing could erroneously be thought unnecessary.  Procedures for functional appraisal are available, 105 and a  harmonised  protocol  for  assessment  of  developmental  neurotoxicity  was  developed  under  OECD  auspices  in  1999, 106 although a revision is still under review.  

The number of chemicals that can cause neurotoxicity in  laboratory studies probably exceeds 1000, which is far more  than  the  estimated  200  that  have  caused  documented  human neurotoxicity. However, in the absence of systematic  testing, 28  the  true  extent  of  the  neurotoxic  potential  of  industrial chemicals is unknown. The physiology of brain  development 12–14  and  experimental  evidence14,26,27  suggest  that developmental neurotoxicity is likely for all of them,  except perhaps for some of the compounds that require  metabolic transformation to become neurotoxic, in which  immature  metabolism  may  provide  some  degree  of  protection. 19,107 The few substances proven to be toxic to  human neurodevelopment should therefore be viewed as  the tip of a very large iceberg (figure 2).

 Large-scale, prospective epidemiological studies, such  as birth cohorts from Europe 108 and the National Children’s  Study proposed in the USA, will be especially informative  about  early  toxic  exposures  and  neurodevelopmental  disorders. 109  Data  from  these  investigations,  especially  when  pooled  internationally,  will  hopefully  provide  dose-response associations that can guide future disease  prevention  efforts.  This  research  should  move  beyond  repeated assessments of known neurotoxins to examine  chemicals,  whose  toxicity  is  just  beginning  to  be  recognised. The substances listed in the panel, especially  those most prevalent in food, drinking water, and the  environment,  should  provide  a  useful  starting  point.  Nevertheless,  these  initiatives  could  take  decades  to  generate the type of detailed documentation required for  chemicals regulation.

The Food Quality Protection Act in the USA requires  that pesticide standards be set at values that will protect  infants against developmental toxicity. If testing data are  not available, a child-protective safety factor should be used  in standard settings. However, application of this factor  has  been  uneven,  and  regulatory  authorities  need  to  recognise the vulnerability of prenatal brain development.

 Prevention of neurodevelopmental disorders of chemical  origin  will  need  new  approaches  to  control  chemical  exposures. The vulnerability of the human nervous system  and  its  special  susceptibility  during  early  development  suggest that protection of the developing brain should be a  paramount goal of public health protection. The high level  of  proof  needed  for  chemical  control  legislation  has  resulted  in  a  slow  pace  of  interventions  to  prevent  exposures to lead and other recognised hazards. Instead,  exposure limits for chemicals should be set at values that  recognise the unique sensitivity of pregnant women and  young children, and they should aim at protecting brain  development. This precautionary approach, which is now  beginning to be used in the EU, would mean that early  indications of a potential for a serious toxic effect, such as  developmental  neurotoxicity,  should  lead  to  strict  regulation, which could later be relaxed, should subsequent  documentation  show  less  harm  than  anticipated. 110  As  physicians, we should use prudence when counselling our  patients, especially pregnant mothers, about avoidance of  exposures  to  chemicals  of  unknown  and  untested  neurotoxic potential.

Fluoride References

 89  Mullenix PJ, Denbesten PK, Schunior A, Kernan WJ. Neurotoxicity  of sodium fluoride in rats. Neurotoxicol Teratol 1995; 17: 169–77.

 90  Xiang Q, Liang Y, Chen L, et al. Effect of fluoride in drinking water  on children’s intelligence. Fluoride 2003; 36: 84–94.  

91  Lu Y, Sun ZR, Wu LN, Wang X, Lu W, Liu SS. Effect of high-fluoride  water on intelligence in children. Fluoride 2000; 33: 74–78.

92  Qin LS, Cui SY. The influence of drinking water fluoride on pupils’  IQ as measured by Rui Wen’s standard [in Chinese].  Chinese J Control Epid Dis 1990; 5: 203–04.
———————————————
Article from: The Associated Press

Pollution poisons children

http://www.news.com.au/dailytelegraph/story/0,,20729512-5006007,00.html

By John von Radowitz

November 10, 2006 12:00

MILLIONS of children worldwide may have suffered brain damage as a direct result of industrial pollution, scientists say.

An explosive report  talks of a “silent pandemic'’ of neurodevelopmental disorders caused by toxic chemicals spilling into the environment.

They include conditions such as autism, attention deficit disorder, mental retardation and cerebral palsy.  All are common and can result in lifelong disability, but their causes are largely unknown.

The scientists, from Holland and the US, identified 202 industrial chemicals with the potential to damage the human brain, and said they were likely to be the “tip of a very large iceberg'’. More than 1,000 chemicals are known to be neurotoxic in animals, and are also likely to be harmful to humans.

The researchers made an urgent call for much tighter worldwide controls on chemicals, and a “precautionary approach'’ to testing. Dr Philippe Grandjean, from the Department of Environmental Medicine at the University of Southern Denmark in Winslowparken, one of the study’s two authors, said: “The human brain is a precious and vulnerable organ.

“And because optimal brain function depends on the integrity of the organ, even limited damage may have serious consequences. Even if substantial documentation on their toxicity is available, most chemicals are not regulated to protect the developing brain. Only a few substances, such as lead and mercury, are controlled with the purpose of protecting children.

“The 200 other chemicals that are known to be toxic to the human brain are not regulated to prevent adverse effects on the foetus or a small child.'’ Grandjean and co- author Professor Philip Landrigan, from the Mount Sinai School of Medicine in New York, trawled a range of scientific data sources to compile their evidence.

Five substances for which sufficient toxicity evidence exist were examined in detail - lead, methylmercury, arsenic, polychlorinated biphenyls (PCBs) and toluene. In each case, the dangers came to light the same way.

First, there was a recognition of high dosage toxicity in adults, and records of isolated episodes of poisoning among children. This was followed by a growing body of epidemiological evidence that lower levels of exposure in children led to neurobehavioral defects.

Pinning down the effects of industrial chemical pollution is extremely difficult because they may not produce symptoms for several years or even decades, said the scientists. This was why the pandemic is “silent'’. The damage caused by individual toxic chemicals is not obviously apparent in available health statistics.

But the extent of the sub-clinical risk to large populations is illustrated by the legacy of lead. Virtually all children born in industrialised countries between 1960 and 1980 must have been exposed to lead from petrol, said the researchers. Based on what is known about the toxic effects of lead, this may have reduced exceptional IQ scores of above 130 by more than half, and increased the number of scores less than 70.

Other results of lead exposure included shortened attention span, slowed motor coordination and heightened aggressiveness. In later life, early damage from lead can increase the risk of Parkinson’s and other neurodegenerative diseases.

Today, it is estimated that lead poisoning in children costs the US economy $A55 billion each year. One in six children is thought to have some kind of developmental disability, usually involving the nervous system.

Developing brains are much more susceptible to toxic chemicals than those of adults, pointed out the scientists. Interference with complex changes taking place in the developing brain can have permanent consequences. And research had shown that this vulnerable period lasts from the foetal stage of life through infancy and childhood to adolescence.

Writing in the online version of The Lancet medical journal, the scientists conclude: “The combined evidence suggests that neurodevelopmental disorders caused by industrial chemicals has created a silent pandemic in modern society.

“Although these chemicals might have caused impaired brain development to millions of children worldwide, the profound effects of such a pandemic are not apparent from available health statistics. Additionally … only a few chemical causes have been recognised, so the full effects of our industrial activities could be substantially greater than recognised at present.'’

In the EU, 100,000 chemicals were registered for commercial use in 1981, and in the US, 80,000 are registered. Yet fewer than half had been subjected to even token laboratory testing, said the report, and in 80 per cent of cases there was no information about potential danger to children.

Although new chemicals went through more rigorous testing, access to the data could be restricted for commercial reasons. In the EU, a new testing program called Reach is planned under proposed legislation that will enforce tighter controls.

But the scientists said that even this does not go far enough, since it fails to emphasise the importance of testing chemicals for developmental neurotoxicity. “Toxicity testing protocols for chemicals need to be expanded to include examination of neurobehavioral functions,'’ they said.

There was a mixed reaction to the research from other experts.

Professor Mark Hanson, director of developmental origins of health and disease at Southampton University, said: “The authors have put their finger on something which is important and which will not go away. The review, in a way, is timely because it will stir up debate and hopefully generate more research in this area. There is no need to panic, but we can’t ignore this possible problem.'’

Professor Alan Boobis, from the section of experimental medicine and toxicology at Imperial College London, said: “The authors of this review have raised an issue of significant concern, but some of the evidence in support of the conclusions lacks rigour. This is a risk management issue. In implementing the precautionary principle, it is important to take into account all relevant information and not just the potential harm that might result from inaction.'’

Professor Nigel Brown, head of the faculty of medicine and biomedical sciences at the University of London, criticised the report, saying the authors “verge on scaremongering'’. He said: “From their assertions, the authors conclude that the combined evidence suggests that neurodevelopmental disorders caused by industrial chemicals has created a silent pandemic in modern society. This is a gross overstatement.

“It is possible that there is a problem. We should be aware of this and we should study the problem, but there is currently not a shred of evidence of a pandemic.'’