Wednesday, May 30, 2012

Neurotoxicity and Violent Crime: Linking Brain Biochemistry, Toxins, and Violent Crime




Professor Roger D Masters
ABSTRACT


         Social scientists who dismiss evolutionary psychology seem unaware that a revolution in neuroscience and other areas of biology has taken place over the last half-century.  The estimate of 83 million Americans taking drugs like Prozac for depression and 11 million children on Ritalin for hyperactivity indicate it is time to reconsider the role of brain chemistry in social behavior and violent behavior.   As evolutionary psychology demonstrates, aggressive impulses are an integral part of the primate behavioral repertoire.  Since it is obvious that loss of impulse control can contribute to violent outbursts and evidence shows that some toxic chemicals (such as lead) can have this effect, it is time to consider neuroscientific evidence linking environmental toxins and rates of violent behavior.  To illustrate the implications of the new issues involved, I focus on a public policy that inadvertently seems to increase rates of violent crime.   Two chemicals (H2SiF6and Na2SiF6, jointly called “silicofluorides” or SiFs) are used to treat public water supplies of 140 million Americans even though, as the EPA has admitted, they have never been adequately tested for safety.  To illustrate the interdisciplinary complexities entailed when linking brain chemistry to policy decisions concerning violent crime, this analysis has four main stages: first, why might SiFs be dangerous? Second, what biochemical effects of SiF could have toxic consequences for humans?  Third, on this basis a research hypothesis predicts children in communities using SiF should have increased uptake of lead from environmental sources and higher rates of behavioral dysfunctions known to be caused by lead neurotoxicity.   Finally, since violent behavior is one of the effects of lead neurotoxicity, the hypothesis is tested using multiple sources of data including rates of violent crime studied using a variety of multivariate statistical techniques (including analysis of variance, multiple regression, and stepwise regression).   As should be obvious, a combination of interdisciplinary perspectives and great prudence is needed to link research in neuroscience and toxicology to policies concerning violent crime,    If confirmed, however, such hypotheses reveal the generally unsuspected value of analyzing human social behavior and public policy from the perspective of evolutionary psychology.

NOTE: The research reported here was done in collaboration with Myron J. Coplan, who suggested we work together on silicofluoride toxicity.    For his chemical analysis of the toxicity of silicofluorides from the perspective of an experienced chemical engineer, see the Appendix: "Silicofluorides are Harmful Toxins."

I. Introduction


         Although recent neuroscientific research has revolutionized our understanding of brain function, studies in this field usually focus on the individual CNS.  This emphasis has been necessary given the immense complexity of cytoarchitecture, neurochemistry, and function.  Now, however, it is time to link our growing knowledge of brain function and evolutionary psychology to public policy.    Such a linkage, with a particular focus on the links between neurotoxins and violent crime, shows the growing importance of evolutionary psychology, which – unlike earlier psychological theories – provides a solid framework for understanding new findings in neuroscience, toxicology, and behavior. 

         A. Evolutionary Psychology and Violence

         Evolutionary psychology teaches that human behavior needs to be understood in the perspective of hominid evolution and behavioral biology.   In addition to describing the repertoire of primate social behaviors as well as the likely developments associated with the appearance of hominids over the last 100,000 years, evolutionary psychology is open to insights from genetics, neuroscience, and ecology.   As experience teaches us only too well, individuals differ in behavioral propensities for reasons that include genetic predispositions, personal experiences and environmental contingencies. 

         Unlike classical behaviorism, for example, evolutionary psychologists recognize a species-typical repertoire of behavior that includes threat and aggression as well as communication, bonding, sexuality, and other behaviors such as those linked with hunting and gathering.   This approach, which integrates nature and nurture, facilitates analysis of the characteristic brain structures and neurotransmitter functions associated with distinct behavioral patterns in diverse situations.  From this perspective, while it is important to understand the individual and environmental conditions that elicit particular behaviors, it is equally important to consider inhibitory processes.   Even more important, by integrating ecological factors in behavioral analysis, evolutionary psychology makes it possible to reconsider how economic activities and public policies can modify the environment in ways that have unintended effects on individual behavior.
 
         One promising area for such analyses concerns the harmful effects of toxins on brain chemistry and behavior.[i] Lead, for example, lowers intelligence and learning ability, as Ben Franklin learned from British printers.[ii]   More recently, neurotoxicologists have shown an association between lead uptake and poor impulse control, learning disabilities, and violence,[iii][iv] ,  [v],  [vi] ,   [vii],  [viii],  [ix] , [x] ,  [xi][xii]     In many instances, exposure to lead and other toxins is due to human activities and can be exacerbated by governmental policies.[xiii]   As a result, could differences in rates of violent behavior be traced to brain dysfunction that is made worse by ill-advised legal or bureaucratic decisions?[xiv]

         From the perspective of evolutionary psychology, aggressive impulses and violent behaviors are part of the human behavioral repertoire.   Among hominids, as in the social behavior of other primates, in addition to violent actions directed at potential predators, such behaviors sometimes occur between conspecifics.   Although threat displays often occur within a band (especially in the context of behaviors that establish and maintain social dominance), within group bonding usually inhibits violent outcomes from aggressive interactions.  In contrast, between group competition seems more likely to lead to a violent attack.  On the one hand, aggressors may seek to deprive members of another band of access to crucial resources; on the other, individuals – and especially high status males – sometimes respond to between-group threat with what has been classified as kin-based altruism.   In short, from the perspective of evolutionary psychology, violent behavior is an element in the human repertoire that is normally inhibited within bonded groups but more likely to occur when directed to external threats to families or communities.

         In a civilized society, the acts classified as “violent crime” represent a different form of aggressive behavior.    Social norms and laws establish expectations that include those acts of within-group violence that are customarily inhibited by individuals experiencing aggressive impulses toward others.    Consider two examples in terms of evolutionary psychology.   First, I see a masked man approaching my house with a drawn revolver at 8PM, take out my own gun and shoot him as I open the door.   This violent behavior could well be judged as an act of self-defense rather than a crime.  Second, I see a salesman selling trinkets approaching my house at 2PM on a sunny afternoon, take out my gun and shoot him as I open the door.   In this case, I would probably be accused and convicted of murder.  The first case is violent behavior acceptable if it can be judged under norms founded on the impulses of individual survival and defense of one’s family.  The second is violent crime if judged under norms that include civility to strangers and inhibition of aggressive impulses where no threat is involved.         From this perspective, when analyzing violent crime, evolutionary psychology can both clarify motives and – more important – explain the failure to inhibit aggressive impulses that can trigger illegal violent behavior.    And in addition to genetic predisposition and brain structure, recent research shows that the effects of toxins on neurotransmitter function are often a factor that can undermine normal inhibition of aggression. [xv]     In the development of evolutionary psychology, this level of analysis may be especially important because it often reveals causal patterns that other psychological and sociological theories can neither predict nor explain.

         B. Brain Chemistry, Environmental Toxins, and Violent Crime

         Although the link between brain chemistry and violent crime has seemed implausible to some social scientists, evidence that reduced exposure to toxins can lower the frequency of crime and other costly behaviors is provided by the Congressional ban on the sale of leaded gasoline.[xvi] In this case, the harmful effects of lead pollution from gasoline were apparently strongest during infant’s early neurological development.  While the correlation between each year’s sales of leaded gasoline (as a measure of average exposure to fumes from tetraethyl lead) and that year’s crime rate is virtually nil, the correlation rises sharply as the time lag between leaded gas sales and violent crime rates is extended;  with a lag of 17 years, the correlation is over 0.90 (Table 1).   Since children 17 years or younger rarely engage in violent crime, the very high correlation between lead gas sales and violent crime rates 18 to 26 years later points to fetal or neonatal exposure to lead as a significant but not generally noted factor in violent crime.   As a result, these data can be interpreted to indicate that the drop in U.S. homicide rates since 1991 were facilitated by the Congressional ban on leaded gasoline.[xvii]

         Exploration of such questions is important because behavioral dysfunctions associated with neurotoxicity are often attributed to the individual’s choice, education, or other personal defects.   This tendency is noticeable even when the problem has been traced to a defect that is clearly beyond voluntary control.   Several years ago, for instance, I presented a seminar on “Neuroscience and Learning” at the Harvard Graduate School of Education.  At that time, three participants asserted that hyperactivity and other learning disabilities do not exist as CNS deficits but are merely “moral” failings of unruly children.  

The consequence of the gap between neuroscientific findings and our educational system is often costly.  In classes at Dartmouth College, it has not been unusual to discover about one student out of every ten with a previously undiagnosed learning disability.   Indeed, when Science published an analysis of brain function among dyslexics in three countries,[xviii]  the PET scans showing the brain loci not active among dyslexic children seem to have been – for some educators – the first concrete evidence that this condition has a basis in brain function.

         Even where hyperactivity and learning disabilities are viewed as needing treatment, the neurological factors that might underlie each child’s problem are often ignored.   To be sure, a specific learning disability or behavioral problem may be traced to various factors.  Among CNS characteristics that have been linked to hyperactivity (ADHD) are damage to a specific brain structure (the Nucleus Accumbens)[xix] as well as deficits in dopaminergic or serotonergic activity.[xx]  Where neurotransmitter dysfunction is implicated, lead toxicity is often one of the factors involved.[xxi]  Given evidence that ADHD is a "spectrum disorder" (i.e., symptions cover a range of deficits), the co-occurrence of multiple risk factors could easily explain some of these variations.

 

BECAUSE HYPERACTIVITY DUE TO A LOSS OF IMPULSE CONTROL CAN ALSO BE OBSERVED IN VIOLENT BEHAVIOR, THE ROLE OF NEUROTOXINS IN ADHD DESERVES SPECIAL ATTENTION.  ALTHOUGH EXCESSIVE CELLULAR UPTAKE OF LEAD CAN BE TREATED BY CHELATION, TEACHERS AND PHYSICIANS OFTEN GIVE HYPERACTIVE CHILDREN MEDICATIONS LIKE RITALIN WITHOUT SCREENING FOR OTHER KNOWN RISK FACTORS.  IN THE U.S. ALONE, IT HAS BEEN ESTIMATED THAT AS MANY AS 11 MILLION CHILDREN ARE RECEIVING RITALIN OR OTHER DRUGS WHICH IMPROVE BEHAVIOR BY ACTIVATING INHIBITORY CIRCUITS IN THE BRAIN (SUCH AS DOPAMINERGIC PATHWAYS IN THE BASAL GANGLIA).    FOR ADHD CHILDREN, SUCH MEDICATIONS PROVIDE A “QUICK FIX” THAT MASKS UNDERLYING PROBLEMS AND CREATES A DANGER OF LONG-TERM DRUG ABUSE FROM A “MEDICATION” THAT HAS EFFECTS PARALLEL TO THOSE OF COCAINE.[XXII]     INDEED, JOURNALISTIC REPORTS THAT RITALIN HAS BECOME A POPULAR RECREATIONAL DRUG UNDERSCORE THE NEED TO ADOPT A MORE SCIENTIFIC APPROACH TO THE ANALYSIS AND TREATMENT OF LEARNING DISABILITIES OR BEHAVIORAL PROBLEMS WITH AN IDENTIFIED NEUROLOGICAL BASIS.  OBVIOUSLY, SUCH USES OF RITALIN CAN MASK THE PROBLEM AND COULD ACTUALLY INCREASE THE RISKS OF VIOLENT BEHAVIOR IN LATER YEARS.


         Dealing with such issues is unlikely to be successful unless neuroscientific research is linked with the social dimensions of environment, individual behavior, and public policy.    To illustrate the potential of such an approach, we here present evidence of the neurotoxic effects of two largely untested chemicals that are currently added to the drinking water consumed by over 140 million Americans.   These compounds – hydrofluosilicic acid (H2SiF6) and sodium silicofluoride (Na2SiF6) – are more generally called “silicofluorides” (SiFs).[xxiii]    Despite their widespread use, SiFs have never been properly tested for safety; as an EPA official put it, his agency has no evidence on “the health and behavioral effects” of silicofluorides.[xxiv]    

Because the public policy decisions responsible for this situation are not relevant for present purposes,[xxv]  this article will focus on a series of questions that are essential in attempts to link neuroscience and evolutionary psychology to violent behavior.  First, what characteristics of the suspected chemicals make the inquiry plausible and indeed necessary? (Part II: “Why Silicofluorides May be Harmful to Humans”).   Second, based on known effects of these chemicals, what mechanism could trigger neurotoxic harm to humans? (Part III: “Biochemical Effects of Silicofluoride: Mechanisms of Neurotoxicity”).   These two steps culminate in the description of biochemical mechanisms that are predicted to have specific biological and behavioral consequences including increased risks of violence.  Finally, given the research hypothesis developed to this point, is there empirical evidence consistent with the predicted effects? (Part IV: “Testing the Hypothesis: Enhanced Lead Uptake and Behavioral Dysfunctions due to SiF”).    As this outline suggests, in addition to building on research linking evolutionary psychology to neuroscience, analysis of this sort will also require knowledge of such disparate fields as chemistry, toxicology, and public policy.



II. Why Silicofluorides May Be Harmful to Humans


         In the mid 1940’s, the injection of sodium fluoride (NaF) in public water supplies was initiated in the United States as an experiment to ascertain whether rates of tooth decay would be reduced by fluoridated drinking water.   In 1950, midway through a projected 10-12 year experiment, the U.S. Public Health Service authorized the substitution of SiFs for NaF.  Although tests had been conducted on NaF but not on SiFs, the implications of this shift have been generally ignored by both supporters and critics of public “fluoridation” of water supplies.[xxvi]

Whereas NaF hydrolizes on injection into water, completely dissociating fluoride ion from sodium, no empirical evidence of dissociation rates of SiFs at 1 ppm  was available when they were formally approved in 1950.    At that time, the use of SiF was justified on the basis of a theoretical  argument by P. J. McClure (of the Public Health Service) that the dissociation of SiFs would be “virtually complete.”[xxvii]    Twenty-five years later, German laboratory studies by Westendorf revealed major differences between SiF and NaF.  Under conditions comparable to those of a water treatment plant, SiFs are incompletely dissociated and their residues have significant experimental effects on vital enzymes, including acetyl-cholinesterase (AChE) and serum cholinesterases  (or Pseudocholinesterases),  including butyryl-cholinesterase (BCh E).[xxviii]  

Despite recent assertions of two EPA scientists (Urbansky and Schock),[xxix] this difference between NaF and SiF is consistent with other experimental findings.   SiF anion [SiF62- remains intact at pH 7 at room temperature.  It must be exposed to boiling water at pH 9 in order to effect total fluoride release so that no residues of partially dissociated SiF remain in solution.  Moreover, since the dissociation process is reversible, reassociation of SiF from its components is possible (for example, when SiF treated water is used in cooking).  Hence the assumed identity of NaF and SiF, which persists in many discussions of public health and dentistry[xxx][xxxi],[xxxii] and was reinforced in the CDC’s recent publication of a study group’s “Recommendations” on Fluoridation,[xxxiii] can no longer be sustained without disconfirming existing research on these compounds.

When Westendorf set out to study SiF dissociation under more realistic conditions than had been tried previously, he used a refined technique.  Measuring fluoride ion released from SiF at physiological conditions (pH 7.4, 37 oC) in Ringer’s solution at 1-5 ppm of total fluoride, Westendorf could only detect 67% of that fluoride with the fluoride ion specific electrode. He proposed that the remaining fluoride was still bound in a partially dissociated residue of SiF in the form of [SiF2(OH)42-. Whether or not that particular species was the only SiF dissociation residue, Westendorf’s finding was evidence for the survival of some partially undissociated SiF residue.

Translated into water plant parameters, Westendorf’s findings would mean that dilution of SiFs to the 1 to 2 ppm level used in water fluoridation at the pH and temperatures customarily obtaining in the water plant, would induce each [SiF62- ion to release only 4 fluorides to be replaced by hydroxyls. The concentration of resulting SiF dissociation residue [SiF2(OH)22-would be in the order of 1-5 ppm by weight. (Incidentally, the same quantitative release of fluoride from SiFwould correspond with leaving behind the non-ionic species SiF2(OH)at about the same concentration).

Thus, contrary to the total release of fluoride from SiF at water plant conditions assumed by supporters of fluoridation as a public policy,[xxxiv] Westendorf found only 2/3rds fluoride release by actual experiment.     Hence, at a pH close to common water plant practice, Westendorf’s experiments show that SiFs are incompletely dissociated when injected in a public water supply and that the resulting residual complexes can have significant biochemical effects.

These characteristics of SiFs indicate that a harmful chemical may currently be distributed in the public water supplies of many communities in the absence of extensive testing of SiF safety.   The scale of the potential problem is sufficient to justify concern, since over 90% of  water fluoridation in the U.S. uses SiFs.   With over 140 million Americans exposed to them,[xxxv] it is prudent to examine whether SiF residues or other harmful consequences of SiF injection in public water supplies (including the potential for reconstituting SiF in cooking or digestion) have neurotoxic effects that could modify behavior.




III. Biochemical Effects of Silicofluorides and Mechanisms of Neurotoxicity[xxxvi]


A. Enzymatic Inhibition

            That SiF and NaF have different enzymatic effects was shown long before Westendorf completed his laboratory studies in 1975.    In 1933, when reporting on his doctoral research, F. J. McClure reported that fluoride (in the form of NaF) can act as an enzyme inhibitor.[xxxvii]

      Experimental evidence has established the fact that there is also a specific
      influence of fluorides on certain enzymatic changes associated particularly
      with carbohydrates and fats. Thus, the results of a systematic study conducted by
      Kastle and Loevenhart on the effect of antiseptics on the reactions of pancreatic
      and liver extracts revealed an effect of most substances and also a particularly
      remarkable destructive action of NaF on the reaction of lipase...Dilutions of
      NaF as low as 1:15,000,000 [0.07 ppm] may inhibit the action of lipase on
      ethyl acetate as much as 50 per cent…Leake et al have obtained evidence that
      NaF inhibits the action of this enzyme in vivo.” [xxxviii]

Two years later (in 1935), Kick et al. found the excretion pathways of fluoride differ depending on whether test animals have ingested NaF or SiF.[xxxix]   

Little additional work on the biological effects of these chemicals was conducted until Westendorf found that SiF inhibits AChE without a concentration threshold, whereas NaF inhibition of AChE starts at about 5 ppm of fluoride ion.  Moreover, at equal fluoride levels beyond the NaF threshold level, SiF is about 2-4 times more powerful an inhibitor of AchE than NaF. The kinetics indicated that NaF inhibition was only competitive (i.e., worked by blocking the enzyme active site), while SiF inhibition was both competitive and non-competitive.

Competitive inhibition is explained by the presence of hydrofluoric acid (HF), formed from free fluoride ion, which could find and occupy the active site in the enzyme molecule. That would occur whether inhibition were due to NaF or SiF, since both release free fluoride under physiological conditions at 1 ppm of fluoride. However, whereas NaF releases all of its fluoride ion by simple dilution/ionization, SiFs release fluoride ion in a complicated sequence of dissociation steps that depend on concentration and pH.

The chemical structures of likely SiF residues  -- [SiF2(OH)4]2-or SiF2(OH)2 --  would make each one a logical precursor for the creation of mono-silicic acid in the blood-stream.   Mono-silicic acid is not a commonplace form of hydrated silica in blood and according to the following hypothesis, has the potential for serious damage to health and behavior in a number of ways.

B. Residual Complexes Due to Incomplete Dissociation

Myron Coplan, the chemist with whom I collaborated on this research, explains the chemistry as follows.[xl]  A partially dissociated monomeric SiF species either survives into the stomach or is re-formed there at gastric pH. It then passes into the blood-stream where it hydrolyzes to mono-silicic acid and/or forms low molecular weight silicic acid oligomers. These readily bind via their silanol hydroxyls to any polypeptide backbone with a reactable amine or hydroxyl. That alone would interfere with normal polypeptide structure and function. However, subsequent reaction of as-yet unreacted pendant silanols with one another would also create siloxane bonds or more linkages to the polypeptide backbone in such a way as to disrupt the natural chain folding of proteins.

A recent report amplifies this hypothesis and adds significantly to its credibility:
      
         “The polymerization of silicic acid in aqueous solutions at different pH was
           followed by the colorimetric molybdosilicate method. The role of four
           amino acids (serine, lysine, proline and aspartic acid) and the corresponding
           homopeptides was studied. All four amino acids behave the same way and favor
           the condensation of silicic acid. Peptides exhibit a stronger catalytic effect
           than amino acids but they appear to behave in very different ways depending
           on the nature of side-groups and pH. Poly-lysine and poly-proline for instance
           lead to the precipitation of solid phases containing both silica and peptides. The
           role of these biomolecules on the polymerization of silicic acid is discussed in
           terms of electrostatic interactions, hydrogen bonds and solubility.”[xli]

This report supports the proposition that silicic acid reaction with blood proteins could well be the root cause for SiF’s powerful inhibition of AChE and “pseudo-cholinesterases” (PChEs), which are also known as “serum cholinesterases” and include butyryl-cholinesterase (BChE).

C. Effects of Cholinesterase Inhibition

The implications for human health of this SiF-induced bio-mechanism are numerous and in some instances can be extremely serious.  One of the most important of these effects concerns the interference with cholinesterases.   While acetylcholinesterase (AChE) is known due to its regulatory role for acetylcholine (a neurotransmitter with multiple functions including activating motor behavior), even today the role of butyryl-cholinesterase (BChE) and its relationship to AChE is not entirely understood:

       “Human tissues have two distinct cholinesterase activities: acetylcholinesterase and
         butyrylcholinesterase. Acetylcholinesterase functions in the transmission of nerve 
         impulses, whereas the physiological function of butyrylcholinesterase remains
         unknown.”[xlii]

At least one function believed to be served by BChE is to protect AChE by scavenging toxins.

        “Butyrylcholinesterase must be differentiated from acetylcholinesterase, which
          cannot hydrolyse succinylcholine. The physiological action of butyryl-
          cholinesterase remains unknown, although it can hydrolyse many drugs.”[xliii]

It is not inconceivable that the role of BChE as a protector of AChE goes beyond the capacity to hydrolyze drugs to a sacrificial role in absorbing heavy metals. In any case, powerful inhibition of BChE by SiF would indirectly modify an indirect impact on the proper function of AChE. Moreover, their interaction has been associated with brain dysfunction:

       “Evidence about nonclassic functions of acetyl- (AChE) and butyryl-cholinesterase
         (BChE) during embryonic development of vertebrate brains is compared with
         evidence of their expression in Alzheimer disease (AD). Before axons extend
         in the early neural tube, BChE expression shortly precedes the expression of
         AChE. BChE is associated with neuronal and glial cell proliferation, and it may
         also regulate AChE. AChE is suggested to guide and stabilize growing axons.
         Pathologically, cholinesterase expression in AD shows some resemblance to
         that in the embryo.”[xliv]

Regarding AChE inhibition, Westendorf found that fluoride released by NaF acted only in the competitive mode, but SiF had a much more powerful effect and acted in two modes. The first mode was competitive, as expected, due to the 67 % of the SiF fluoride released as free fluoride. In addition, however, the non-dissociated fluoride-bearing SiF residue enhanced net inhibition significantly in the non-competitive mode. Westendorf suggested that the species [SiF2(OH)42- mentioned above somehow distorted the morphology of the AChE molecule but he did not offer an explanation for how that occurred. Without referring to Westendorf’s work at all, a hint of an explanation for this effect appeared in the English language literature a few years later.[xlv]

The “Margolis mechanism” discussed by Iler [xlvi] suggests how low molecular weight poly-silicic acid oligomers formed in the blood-stream could disrupt polypeptide chain morphology:

        “The effect of silica was described by Margolis as due to the adsorption and
         denaturation of a globular protein, the Hageman factor. The proposed mechanism
         was that on sufficiently large particles or on flat  surfaces of silica, the protein
         molecule was stretched out of shape by adsorption forces as it formed a
         monolayer on the surface. When the silica particles were very small, the molecular
         segments of the protein could become attached to different particles without
         segment stretching…When protein is adsorbed on a larger silica particle or a
         coherent aggregate of smaller particles, the chain  stretched and certain internal
         hydrogen bonds which hold the protein molecule in a specific configuration
         are broken. On small single particles no such stretching occurs.”
 
Any of the partially dissociated SiF species just described -- e.g., [SiF2(OH)4]2-, SiF4, or SiF2(OH)2 derived from SiF4 -- would be candidates for producing low molecular weight polysilicic acid oligomers in the blood stream, after crossing over from the stomach at pH around 2. Most enzymes are globular proteins, so many enzymes besides AChE would be likely to experience at least noncompetitive inhibition by the “Margolis mechanism.”


D. Ferry Molecules and Enhanced Heavy Metal Uptake

A wide array of non-enzyme polypeptides whose chain folding determine their function would also be subject to this morphological disruption.  As a result, adverse effects of the partially dissociated SiF residue are not limited to adsorption by globular proteins or on flat surfaces.   Given covalent bonding with any protein hydroxyl and amino sites by silicon-bound fluorine as described above, many other specific polypeptide morphology effects besides enzyme inhibition would also be susceptible to disruption.

         Other mechanisms that enhance lead uptake or modify neurotransmitter function might also exist.  For instance, if undissociated or reassociated SiF reaches the brain, its function as an AchE and BChE inhibitor could reinforce the effects of other cholinesterase inhibitors (such as organo-phosphate pesticide residues).  Since Abou-Donia’s experimental work shows that AChE inhibition has cumulative effects, even relatively small residues might enhance the effect of other toxins in this class.[xlvii]

It is especially noteworthy that Westendorf’s SiF experimental data on incomplete dissociation are consistent with a bio-chemical mechanism that could enhance gut/blood lead transport and hence increase uptake of lead from environmental exposures.   The compound Westendorf postulated as the partially hydrolyzed ionic species [SiF2(OH)42- closely resembles the SiF2(OH)2 molecule that we have proposed as a “ferry molecule” capable of chelating a heavy metal ion via the hydroxyls, with the enhanced ability to permeate lipophilic membranes due to the two residual fluorines.[xlviii]   In addition, the two fluorines still bound to silicon at the 67 % dissociation of SiF found by Westendorf could be due to survival of half hydrolyzed SiF4 molecule as well as to a 2/3rds hydrolyzed [SiF6]2-.

If the strong non-competitive enzyme inhibition by SiF found by Westendorf was the result of disruption of protein chain folding by low molecular weight polysilicic acid oligomers, a partly hydrolyzed SiF4 molecule would be as likely to have that effect as the [SiF2(OH)42- anion. Defective protein morphology could result by the adsorption process suggested by Margolis or by covalent bonding between active silicon-fluorine bonds in partially-dissociated SiFs with blood proteins.

The result could be the formation of molecules that can “ferry” a toxin like lead to the brain or other organs, thus shortcircuiting such natural detoxification enzymes as glutathione or metallothionines.  Prior to Westendorf’s research in Germany, although there was evidence that SiF had potentially harmful effects not found for NaF, there is little indication that American researchers were aware of this possibility.[xlix] The shift from NaF to SiFs as fluoridation agents was endorsed in 1950, at which time no one could have known of Westendorf’s findings (first partly revealed in 1974, when Naturwissenschaft carried a brief account of the findings more fully reported in Westendorf’s thesis in 1975).[l]   The situation today differs due to the radical advances in neuroscience combined with the availability of extensive empirical evidence (including the English translation of Westendorf’s thesis).

         Under these circumstances, it is now reasonable to test the hypothesis that children living in communities with SiF treated water are more likely to absorb lead from their environment, and to exhibit behaviors that have been linked to lead neurotoxicity or cholinesterase inhibition.   Because the Center for Disease Control monitors the chemicals used in water fluoridation, if geographic data is sufficiently precise it can be used to test these hypotheses.  Four types of data were available for statistical analysis: 1) the chemicals used for water fluoridation in each community; 2) children’s blood lead levels from either state health surveys or the National Health and Nutrition Evaluation Survey (NHANES III), 3) socio-economic and ecological data from the U.S. Census, and 4) rates of violent crime as reported by the FBI.   We began, therefore, by examining whether SiF usage is associated with enhanced uptake of lead from such environmental sources as old housing with lead paint or high lead levels in public water supplies (obviously, the absence of significant effects at this level would falsify the hypothesis).  Then, having confirmed that blood lead uptake reflects something akin to the proposed “ferry molecules” or residual complexes due to SiF water treatment, we test whether the use of silicofluorides is associated with increased rates of behavioral dysfunctions linked to blood lead, focusing on violent crime and substance abuse by criminals.


IV.  Testing the Hypothesis:  Enhanced Lead Uptake and Behavioral Dysfunctions due to SiF

         To assess predictions of social phenomena based on neuroscientific and toxicological findings at the individual level, it is necessary to examine aggregate data with care.  Geographically diverse samples of individuals need to be studied using multivariate statistical techniques to control for the effects of potentially confounding variables.     More than one sample should be studied, and samples should be large enough to insure that tests of statistical significance are meaningful.  For any one sample, moreover, it is useful to analyze the data in more than one way, using different statistical techniques (such as multiple regression, logistic regression, and analysis of variance) and examining subsamples to explore the incidence of observed effects among individuals of different race, age, or sex.  Finally, but of particular importance, it is important to examine aggregate data both for a biological effect known to influence behavior (e.g., levels of blood lead as a test of uptake of a dangerous neurotoxin) and for behaviors that might have been made more likely by the toxin (e.g., substance abuse and violent crime).

Multiple analyses are therefore necessary to test the hypothesis that SiF treated water exposes individuals to residues that enhance lead uptake (such as the “ferry molecules” described above) and thereby increases rates of behavioral dysfunction.  As an illustration of the methodological problems facing any such endeavor, at least four distinct empirical issues need to be addressed.  

A.   Population samples should provide evidence of biological differences between those exposed and not exposed to the presumed source of neurotoxicity.  In the present case, do children living in communities with SiF treated water have, controlling for other variables, higher blood lead levels?

B.   These effects should include evidence consistent with the presumed mechanism.  In the present case, does exposure to SiF increase the risks of high blood lead from such known environmental sources of lead as old housing and lead levels over 15 ppb in public water supplies?

C.     The effects should occur among different types of individuals – and, insofar as there is variation by population sub-groups, the differences should correspond with previously known variations.  In the present case, how does SiF exposure affect blood lead levels among children of different races and ages – and, in particular, how do these effects relate to the generally higher blood lead levels usually found among Blacks in the U.S.?

D.   Behaviors previously linked to the toxins in question should be more frequent in times and places where the environmental problem of interest is present.  In the present case, are rates of crime and substance abuse higher in communities using SiF than in comparable localities whose water is not treated with these chemicals?

The first three questions will be explored using several geographic samples for which we have data on children’s blood lead levels (usually based on samples of venous blood lead as well as capillary blood lead).    First, for the state of Massachusetts, we have a data from capillary blood lead tests of children in 213 communities (constituting virtually all localities with a population over 3,000, including all but one of the communities using SiF treated water).[li]   This sample provided data for approximately 280,000 children, and was analyzed both for all 213 towns and for venous blood lead measurements in a subset of  76,566 children from 30 communities with and 30 communities without SiF treatment [lii]   Second, for the state of New York, we studied a sample of venous blood tests from 151,225 children in 103 communities with populations between 15,000 and 75,000.[liii]   Finally, we examined blood lead data for almost 4,000 children in the National Health and Nutrition Evaluation Survey III (NHANES III) who lived in 35 counties of population over 500,000.[liv]  

Whereas the first two of these samples had data by community, permitting unambiguous evidence of whether or not children were exposed to SiF, the NHANES III data (only available by county) was divided into counties with less than 10% of the population exposed to SiF, between 10 and 80% exposed to SiF, and more than 80% exposed to SiF.  For most purposes, the best assessments here were a contrast between counties with less than 10% SiF exposure (on aggregate, about 6% of children in this category drank SiF treated water) and counties with over 80% exposure (on aggregate, 92% of children in this group drank SiF treated water).

For an epidemiological study of behavioral outcomes, we can then use national FBI county-level data for rates of violent crimes.  This makes it possible to compare counties for the effects of industrial lead pollution and SiF treated water while controlling for socio-economic and demographic factors using census data.  For substance abuse, a sample of over 30,000 criminals in 24 cities studied by the National Institute of Justice (NIJ) was assessed for the association between cocaine use at time of arrest and age of first substance abuse.   While further studies are desirable, it should be evident that these datasets are sufficiently diverse to provide a reasonable test of the twin hypotheses that SiF treated water contains residues (such as the postulated “ferry molecules”) which enhance lead uptake, and that the resulting neurotoxicity is associated with costly behavioral dysfunctions.

A. HIGHER BLOOD LEAD LEVELS WHERE SILICOFLUORIDES ARE IN USE


         In Massachusetts communities using SiF, children’s blood lead levels were higher and the probabilities of a level over 10µg/dL were greater:

Whereas a community's average uptake of lead by children is weakly associated with the so-called "90th percentile first draw" levels of lead in public water supplies (adjusted r2 = .02), the fluoridation agents used in water treatment have a major effect on lead levels in children's blood.  Average levels of lead in capillary blood were 2.78 mg/dL in communities using fluosilicic acid and 2.66 mg/dL in communities using sodium silicofluoride, while they were significantly lower in communities that used sodium fluoride (2.07 mg/dL) or did not fluoridate (2.02 mg/dL) (one way ANOVA, p = .0006; DF 3, 209, F 6.073).  The prevalence rate of individuals whose capillary blood lead was above the maximum permissible level of 10mg/dL was also significantly higher in the communities using either of the silicofluoride compounds (fluosilicic acid = 2.9%, sodium silicofluoride = 3.0%; sodium fluoride = 1.6%; untreated = 1.9%; p < .0001; DF 3,212, F 8.408).  Despite smaller samples tested, similar findings were obtained using venous blood uptake.   These findings are independent of recorded 90th percentile first draw lead levels in the public water supplies.[lv]

Overall, roughly four times as many SiF treated communities as non-fluoridated or NaF treated communities have over 3% children with blood lead over 5µg/dL.  Moreover, these effects are evident where environmental lead sources are below average, but they are exacerbated when lead levels in water or the percent of old houses are above average.  For instance, in communities using sodium fluoride where first draw lead in public water exceeded 15 ppb, average blood lead levels were actually lower (1.9 µg/dL) than in communities using this chemical with less lead in their water (2.11µg/dL).  In contrast, in 25 communities using fluosilicic acid with over 15ppb lead in water, children’s blood lead averaged 3.27 µg/dL compared to only 2.31 µg/dL in 26 communities using fluosilicic acid where lead in 90th % first draw water was under 15ppb.  Effects in a smaller number of communities using sodium silicofluoride were comparable, with blood lead averaging 4.38 µg/dL where first draw lead was above 15ppb (n = 1) compared to 2.37 where lead in water was under 15ppb (n = 6).[lvi]    (For further analysis of the hypothesis that SiF residues enhance uptake of lead from environmental sources such as old housing or lead in public water supplies, see Section IV.B below).

The association between SiFs and higher blood lead was confirmed by comparing a subsample of 30 non-fluoridated Massachusetts communities with 30 matched communities using SiF (Table 2).  Here, although the SiF treated towns had 50% more lead in public water supplies, more poor, and more minorities, they also had slightly higher per capita income, higher elementary school budgets, and a larger percentage of college graduates.  None of these differences fully explain why 1.94% of screened children had blood lead levels in excess of 10µg/dL where SiF was in use, whereas only 0.76% had such high blood lead in the comparable non-treated towns.

New York data are consistent with an association between the use of SiF and higher venous blood lead levels among children. Overall, there was a significantly higher average of children with venous blood lead over 10µg/dL (p = .0001, F 9.l28, DF 3, 104) if water was treated with fluosilicic acid (4.52%) or sodium silicofluoride (4.20%) than if water was untreated (3.78%) or treated with sodium fluoride (3.05%).   Among Blacks tested, 20.6% of the 8,685 exposed to SiF had venous blood lead over 10µg/dL, whereas only 7% of the 9,556 in non-SiF communities had blood lead at this level (with similar effects at different blood lead level cutting points).[lvii]    While communities using SiF had somewhat higher levels of seven risk factors associated with higher blood lead  (Table 3), these sources of lead uptake do not fully explain the results; on the contrary, as hypothesized, SiF enhances lead uptake from environmental sources and hence increases the odds of high blood lead even more where these factors are present (see Section IV.B below).

Data from the Third National Health and Nutrition Evaluation Survey (NHANES III) were only available for the sub set of about 4,000 children living in 35 counties having populations over 500,000.  Using the CDC's 1992 Fluoridation Census, the percent of each county’s population receiving silicofluoride treated water was calculated and each county was assigned to one of three groups.   As noted, the “high” group comprised counties in which a total of 92% of the population received SiF-treated water. The “low” group comprised a population only 6% of which received SiF-treated water.  A relatively small group of counties with "intermediate" exposure comprised a population with about a 50% chance of receiving SiF-treated water.   Controlling at the individual level for covariates usually associated with lead uptake, elevated blood lead was statistically significant (p = 0.001 or better), with High/Low risk ratios in the range of 1.5 to 2.0 depending on age and race.[lviii]


BEnhanced Uptake of Lead from Environmental Sources

         We have predicted that the risk of exposure to environmental sources of lead is significantly higher where SiF treated water exposes children to residues including compounds like the suggested “ferry molecules.”   As a result, mere association between SiF usage and higher blood lead levels is insufficient to test the research hypothesis.  Two-way or three-way analysis of variance (ANOVA), which simultaneously considers the relative association between several predictive variables, can also indicate whether the combination of two or three of these predictors (as measured by the “interaction term” of the ANOVA) has significantly stronger effects than the sum of their independent effects.  Our hypothesis predicts significant interaction terms between SiF usage and such environmental risk factors as lead in public water supplies or paint in old housing.  Conventionally, when a two or three way ANOVA has a significant interaction term, statisticians often give weight to the results because such effects are rarely due to measurement error in one of the variables.

         The data from Massachusetts are clearly consistent with the research hypothesis that SiF treated water carries residual complexes including  “ferry molecules” that enhance lead uptake from the environment:

When both fluoridating agents and 90th percentile first draw lead levels are used as predictors of lead uptake, the silicofluoride agents are only associated with substantially above average infant blood lead where lead levels in water are higher than 15ppm.  This interaction between the use of silicofluorides and above average lead in water as predictors of children's lead uptake is statistically significant (p = .05; DF 3,204, F2.62).  To confirm this effect, we assessed the extent to which silicofluoride usage might increase the risk from lead paint in old housing as well as lead in the water. Towns were dichotomized according to whether they use silicofluoride agents, whether percent of houses built before 1940 was above the state median, and whether 90th percentile first draw water lead was over 15 ppb.   In towns with both more old housing and high levels of lead in water, average blood lead is 3.59 mg/dL in 20 towns where silicofluorides are used, and only 2.50mg/dL (slightly above the average of 2.23 mg/dL) in the 26 towns not using these agents.[lix]

These effects show a tendency for SiF to increase the harmful effects of known risk-factors of blood lead uptake that was confirmed by analyses of other samples.

To assess the overall vulnerability of those in high risk environments in the New York sample, we assigned to each individual a value indicating whether his/her community was above or below the median for each of the seven covariate risk factors in Table 3.  We then used these as co-variates in our analysis, dividing the sample of individuals into those who live in communities with four or fewer risk factors and those who live in communities with five or more risk factors. While exposure to five or more risk factors increases the risk of blood lead above 10µg/dL, exposure to this number of risks where SiF is used more than doubles a child’s chance of having elevated blood lead.    Although lead levels are higher for Blacks than for other races in the sample, in the sample as a whole rates of high blood lead were substantially worse for children exposed to SiF.   As will be shown below, these effects were confirmed by computing age-adjusted logistic regressions of odds ratios for venous blood lead over 10µg/dL for children living in communities using SiF compared to those not using these chemicals.[lx]   

The NHANES III data is less useful for such statistical analyses due to smaller sample size and because organization of data by county makes it difficult to assume that a high level of an environmental variable applies to each child in a given county.  Such limitations reinforce the importance of assessing interaction effects in different racial and age groups of children.


C.  SiF exposure and blood lead levels among children of different races and ages.

Prior studies have generally shown that minorities – and especially Blacks – are particularly at risk for high levels of blood lead.   NHANES III data, showing average blood lead levels for Black, Hispanic, or White children aged 3-5 (Figure 1) and 5-17 (Figure 2) provide a useful urban sample.   For each race and each age, lead levels are significantly higher for children exposed to SiF treated water (p < .0001), with effects of exposure to SiF that are significantly worse for minorities than for Whites, and worse for Blacks than for Hispanics.  

Because a similar effect had already been noted for children in our New York State sample, we sought a more precise measure of the impact of SiF treated water on environmental factors associated with higher blood uptake for Blacks as compared to Whites.    We computed the Odds Ratio for higher blood lead among those exposed versus not exposed to SiF treated water (1.0 equals chances are 50-50 whether water does or does not have these chemicals) for White and Black children living in towns above and below the median for each risk factor.  Logistic regression was used to assess these Odds Ratios.  The results show that SiF treated water consistently increases the Odds of high blood lead, but that this effect is exacerbated where risk factors for high blood lead are above average.  Moreover, as seen in other statistical tests, this enhancement of environmental risks by SiF is much greater for Black children than for Whites.

One way of analyzing the Massachusetts sample suggests this effect may be especially strong.  Consistent with established findings, higher blood lead levels are found in communities with an above average proportion of pre-1940 housing (where lead paint is often found) and in communities with more Blacks in the population.  When silicofluoride use is added to the analysis, however, the higher levels of children’s blood lead usually associated with communities with larger Black populations is onlyfound where there are both more older housing and silicofluorides in water treatment (Figure 3).  From this perspective, the enhanced lead uptake due to exposure to silicofluoride-treated water seems to be a critical factor explaining high blood lead among American Blacks.

In the New York sample, the vulnerability of Blacks is also evident from the effect of exposure to SiF on the proportion of children with various blood lead levels (Figure 4).  Virtually all Black children in the New York sample with blood lead levels over 10 µg/dL lived in SiF communities.  In contrast, about 60% of Blacks with less than 5µg/dL of blood lead lived in communities without SiF.  While it has long been noted that Blacks tend to be more vulnerable to lead uptake (due to characteristics such as low calcium in diet, which is perhaps associated with lactose intolerance), SiF water treatment increases this risk substantially.

Data from the NHANES III sample confirm this effect.   In the counties with fewer percent living in poverty and silicofluorides are NOT in use, there is virtually no difference between the average blood lead levels of Whites (3.62µg/dL) and Blacks (3.90µg/dL).  For similar counties with silicofluoride use, blood lead in White children averages 4.62 µg/dL, whereas it is 5.95µg/dL among Blacks.  Similar increases occur in the counties with above average poverty: in both environments, Blacks are effected more strongly than Whites by SiF treated water.  Hence a two-way ANOVA for the sample as a whole shows that SiF treatment is a significant predictor of higher blood lead (p = .0042, F 6.63), whereas community poverty is not significant (F = .000134).

Similar results for the increased lead from environmental risk factors in Massachusetts indicate that the harmful effects of SiF treated water are not primarily due to toxins in the SiF delivered to water treatment [lxi]plants.[lxii] Rather, mechanisms like that of the postulated ferry molecule or other residual complexes from SiF apparently increase the uptake of lead from old housing and from lead in public water supplies.   Since the policy of water fluoridation has been justified by the poor dental health of minorities, it is ironic that the principal chemicals used for this purpose seem to have especially deleterious effects on Blacks and other minorities.[lxiii]


 

 

D. INCREASED VIOLENT CRIME AND OTHER BEHAVIORAL DYSFUNCTIONS


         Because lead is a neurotoxin that lowers dopaminergic function in the inhibitory circuits of the basal ganglia, it is not surprising that researchers have repeatedly found that higher bodily burdens of lead are linked to increased rates of violent crime.[lxiv]   Individual data to this effect imply that ecological data ought to show that communities with industrial lead pollution are associated with higher rates of violent crime.  Such research reveals effects at thesocial level and illustrates how governmental decisions could improve human health and welfare by reducing the impact of environmental poisons.

Geographic variations in violent behavior had been analyzed before our research turned to SiF.   Since data on individual offenders had indicated that violent behavior could be linked to the toxic effects of lead or manganese, crime rates in 1991 were compared for all U.S. counties with or without EPA reported Toxic Releases of either of these heavy metals (Figure 5).   Using aggregate data for all U.S. counties, both heavy metals significantly contribute to higher rates of violent crime, with a significant “interaction” effect showing that the combination of lead and manganese has a stronger effect than the sum of each toxin separately.   With counties as the unit of analysis, multiple regression equations including other factors associated with crime, including poverty, unemployment and race, indicate that lead pollution was probably an additional contributory factor in 1991 crime rates (Table 4).

It is logical to predict that if lead pollution is a factor in violent crime, and SiF increases the uptake of environmental lead, then using SiF in water treatment should be associated with higher rates of violent crime.   Using a multiple regression model including both lead and manganese pollution (as measured in the EPA’s Toxic Release Inventory) and percent of county receiving SiF treated water as well as socio-economic and demographic factors linked to violent behavior, this prediction was tested for 1985 rates of violent crime in all U.S. counties (Table 5).  The results show not only that SiF usage is a significant additional factor for higher crime rates, but that once SiF is included in the analysis, toxic releases of lead and manganese are no longer significant predictors of county-level violent crime rates.  

Because the choice of variables in a multiple regression model can sometimes influence the outcome, a slightly different set of variables was used in regression equations to predict county level rates of violent crime in both 1985 (Table 6) and 1991 (Table 7).  In both cases, SiF is a significant predictor of violence.  Moreover, the contrast between Tables 4 and 5 indicates that, where SiF is not used in public water supplies, industrial pollution with either lead or manganese has a much weaker impact on violent crime rates. This finding is consistent with the evidence that SiF enhances heavy metal uptake by biochemical mechanisms like those outlined above.

Other population-level tests of behavioral harm due to silicofluoride usage are limited by the lack of reliable measures of conditions such as hyperactivity (ADHD) that have been linked to lead toxicity.    An exception, however, is a National Institute of Justice (NIJ) study of substance abuse by violent offenders.   This study recorded the age of first use of alcohol and drugs as well as drug use at the time of arrest for a sample of over 30,000 criminals from 24 cities.   Such data are especially relevant because BChE has recently been found to “accelerate cocaine metabolism in such a way as to potentially lessen the behavioral and toxic effects of cocaine.”[lxv]    As a result, BChE inhibition by SiF residues would increase the effect of cocaine, leading to the prediction that drug use would be more pronounced among violent offenders in cities that inject SiF in public water supplies.

Once again, the data are consistent with the hypothesis.  In the NIJ sample, controlling for the percent of Blacks in the population (which by itself is never significant), use of SiFs was significantly associated with the average age of the first use of alcohol (p = .06), of PCP (p = .0155), and of Crack (p = .027).[lxvi]  Moreover, the age of first use of alcohol, crack, or cocaine is significantly associated with rates of violent crime (in each case, p < .0001), and crimes rates are significantly higher in the 13 sampled cities using fluosilicic acid (2123 per 100,000) or the 6 cities using sodium silicofluoride (1704 per 100,000) than in the 5 cities not using SiF (1289 per 100,000).[lxvii]  

As a check, rates of drunken behavior per capita were analyzed in our county dataset.  Using step-wise regression to illustrate yet another statistical technique, SiF was one of five variables that significant predicted rates of drunken behavior whereas 7 variables (including the EPA’s Toxic Release Inventory for lead and manganese) had no significant effect on county level rates (Table 8). In all samples studied, therefore, we found evidence that the behavioral effects of SiF residues increase rates of costly behaviors that have previously been linked to lead.  As a result, the evidence suggests that a moratorium on the use of SiF in public water supplies would be a relatively low-cost policy capable of lowering rates of substance abuse and violent crime.  Indeed, given indications that hyperactivity is often linked to lead toxicity, such an initiative might also reduce learning disabilities and improve educational outcomes. 




V. Conclusion

          The foregoing analysis, like the controversy over lowering the permissible levels of arsenic in American public water supplies, suggests that conflicts between science and public policy may be of increasing importance in coming years.  In such issues, the central concern has hitherto been cancer and other mortal diseases.   As our analysis shows, it is now time to link neuroscience, evolutionary psychology, and toxicology to such social behavior as violence.  Just as the ban on leaded gasoline seems to have lowered rates of violent crime since 1991, other initiatives may have substantial benefits by reducing the risks of dysfunctional behavior caused by toxins. 

To illustrate a policy derived from this approach, I have proposed a moratorium on injecting fluosilicic acid or sodium silicofluoride in a public water supply until extensive testing proves their safety.  Such testing is especially necessary for chemicals that are distributed to the general public in a manner not subject to individual choice.  Moreover, since prudent policy initiatives need to consider costs as well as benefits, the use of untested chemicals cannot be justified merely on the presumed benefit to a single medical condition.   It must be stressed that this proposal only concerns the use of fluosilicic acid or sodium silicofluoride in water treatment.  While there is much controversy over the costs and benefits of water fluoridation using sodium fluoride as well, our data does not indicate that NaF is a major factor in enhancing children’s blood lead levels.

In comprehensive cost-benefit analyses of chemicals in our environment, behavioral harm may often be more costly or more widespread than cancer and other mortal diseases.  Indeed, recent studies show that chronic, long term exposure to a low level of a toxin (incuding radioactive substances) can have more serious biological effects than a single, high exposure; called the "Petkau Effect" (after the scientist who first documented it), this process shows the insufficiency of the customary limitation of toxicological studies to a single exposure to the so-called "MCL" ("Maximum Contaminant Level"), which is often set at 50% of the lethal dose.[lxviii]

          The Petkau Effect deserves greater attention because conventional causal models of behavior have often turned out to be unable to explain very important observations of changing behavior patterns.   Most notable recently has been the evidence that rates of violent crime in the U.S. have fallen in recent years.  Good news doesn't seem to interest either social scientists or public policy makers.  One thing that has changed in recent years has been attention to high blood lead levels in children and adults.  That is, greater medical attention to very high blood lead levels may have reduced the frequency of individuals with very high burdens of neurotoxins like lead.   At the same time, moreover, the link between chronic exposure to SiF residues and acetylcholinesterase inhibition may paradoxically help explain the increased visibility of either (or both) ADHD and Alzheimer's Disease.

 As neuroscientists and evolutionary psychologists unravel biological factors in human social behavior, scientists and policy makers in other fields can no longer ignore the costs of learning disabilities, substance abuse, or criminal behaviors that have often proven resistant to traditional treatments or governmental policies based on sociological and economic theories of behavior.    In the era of Prozac, Ritalin, and brain imaging with PET and other technologies, ignoring the revolutionary advances of neuroscientific research is neither prudent nor reasonable.


[i] Gottschalk L, Rebello T, Buchsbaum MS, Tucker HG,  Hodges HL. 1991. Abnormalities in trace elements as indicators of aberrant behavior.Comprehensive Psychiatry  342:229-37


[ii] See the letter from Benjamin Franklin to Benjamin Vaughan “on the bad Effects of Lead taken inwardly” (31 July 1786) in Lemay, ed.,
Complete Writings of Benjamin Franklin  (New York: Library of America, 1987), pp. 1163-1166.

[iii] Herbert Needleman, ed.,  Human Lead Exposure  (Boca Raton, FL: CRC Press, 1989).

[iv] Bryce-Smith D.  1983.  Lead induced disorder of mentation in children.Nutrition and Health.  1:179-94.

[v] Debbie Cory-Slechta, “Relationships between Lead Induced Learning Impairments and Change in Dopaminergic, Cholinergic, Glutamatergic Neurotransmitter System Functioning,” Annual Review of Pharm. Toxic. 35: 3337-395 (1995),

[vi] Needleman HL, Gatsonis B. 1991.  Meta-analysis of 24 studies of learning disabilities due to lead poisoning. JAMA  265:673-78

[vii] Bellinger D, et al.  1994.  Pre-and postnatal lead exposure and behavior problems in school-aged children. Environmental Research.  66:12-30

[viii]Needleman HL.  1999.  Environmental neurotoxins and attention deficit disorder, Presentation at Conference on Environmental Neurotoxins and Developmental Disability, N. Y. Academy of Medicine, New York, May 24-25

[ix] Tuthill RW. 1996.  Hair lead levels related to children's classroom attention-deficit behavior. Archives of Environmental Health.  51:214-20.

[x] Minder B, Das-Smaal EA, Brand, EF,  Orlebeke JM, Jacob F.  1994.  Exposure to lead and specific attentional problems in schoolchildren. Journal of Learning Disabilities. 27:393-98.

[xi] Kahn CA, Kelly, PC, Walker WO. 1995.  Lead screening in children with attention deficit hyperactivity disorder and developmental delay. Clinical Pediatrics. 34:498-501.

[xii] Cook E.H, et al.  1995.  Association of attention deficit disorder and the dopamine transporter gene.  American Journal of Human Genetics, 56,

[xiii] Wollan M. 1968.  Controlling the potential hazards of Government-sponsored technology, Geo. Washington Law Review.  36: 1105-20.

[xiv] For the example to be discussed below, see the web-sitehttp://www.dartmouth.edu/~rmasters/ahabs.htm.

[xv]Masters, R,, Hone, B, and Doshi, A.   (1998).  “Environmental Pollution, Neurotoxicity, and Criminal Violence,” in J. Rose, ed., Environmental Toxicology: Current Developments (London: Gordon and Breach, 1998), pp. 13-48.

[xvi] Kitman Jamie Lee; “The Secret History of Lead. (use of leaded gasoline)”;  The Nation, March 20, 2000 v270.   This article includes especially revealing on the origins of tetrethyl lead usage with knowledge of its toxicity.

[xvii] Masters, Roger D., “Biology and Politics: Linking Nature and Nurture,” in Nelson Polsby, ed., Annual Review of Political Science, Vol. 4 (Palo Alto, CA: Annual Reviews, 2001), pp. 353-356 and esp. Figure 2, p. 356.

[xviii] E. Paulesu, J.-F. Démonet, F. Fazio, E. McCrory, V. Chanoine, N. Brunswick, S.F. Cappa, G. Cossu, M. Habib, C.D.Frith, U. Frith, “Dyslexia: Cultural Diversity and Biological Unity,” Science 291 (17 March 2001), 2165-2167.

[xix] Rudolf N. Cardinal, David R. Pennicott, C. Lakmati Sugathapala, Trevor W. Robbins, Bary J. Everitt.  2001.  “Impulsive Choice Induced in Rats by Lesions of the Nucleus Accumbens Core,” Science 292 (29 June 2001) 2499-2501.

[xx] See references cited in notes 6 and 7 above.

[xxi] Brockel BA, Cory-Slechta DA. 1998.   Lead, attention, and impulsive behavior:  changes in a fixed-ratio waiting-for-reward paradigm. Pharmacology Biochemistry and Behavior.  60:545-52.

[xxii] Sydney Walker, The Hyperactivity Hoax: How to Stop Drugging Your Child and Find Real Medical Help.    (New York: St Martin’s Press, 1998).

[xxiii] See Myron J. Coplan and Roger Masters, Should Silicofluoride Be Used To Fluoridate Municipal Water? Submitted to Congressman Kenneth Calvert, Chair of Subcommittee on Energy and the Environment, Committee on Science, U.S. House of Representatives. April, 2000; idem, Response to EPA Staff Unsupportable Dismissal of Evidence of Adverse Silicofluoride Health Effects. Report to EPA, June 12, 2000; idem, Scientific Misconduct at EPA.  Report to Hon Kenneth Calvert, Chair of Subcommittee on Energy and the Environment, Committee on Science, US House of Representatives, September 25, 2000.

[xxiv] “To answer your first question on whether we have in our possession empirical scientific data on the effects of fluosilicic acid or sodium silicofluoride on health and behavior, our answer is no…. We have contacted our colleagues at NHEERL and they report that with the exception of some acute toxicity data, they were unable to find any information on the effects of silicofluorides on health and behavior.”   Robert C. Thurnau [Chief, Treatment Technology Evaluation Branch, Water Supply and Water Resources Division, U.S. EPA National Risk Management Research Laboratory, Cincinatti, OH] to Roger Masters, Nov. 16, 2000.

[xxv] Andrew Rymer.  The (Political) Science of Fluoridating Public Water Supplies.    Senior Honors Thesis, Dartmouth College, Hanover, NH, 2000; pp. 112 + 14 primary documents

[xxvi] E.g., in 1951, a principal proponent of extending water fluoridation – Francis Bull – explicitly told a dental convention never to mention the chemicals to be used.  This practice has persisted.  For instance, in the recent report onOral Health in the US – 2000, Surgeon General Satcher speaks of “fluoridation” without mentioning the chemicals used.    With few exceptions, critics of water fluoridation have long addressed the issue in similar terms.

[xxvii] McClure, 1950. Years later, several experiments were published that purported to confirm this prediction, but the studies used an ion specific electrode method that required conditions unlike those of a water treatment facility and the reported results rounded figures to the nearest whole number (thereby hiding evidence of incomplete dissociation).

[xxviii] Westendorf  Johannes.  1975.  "Die Kinetik der Acetylcholinesterase hemmung und Die Beeinflussung der  Permeabilitat von Erythrozytenmembranen durch Fluorid und Flurocomplex-Jonen"; Doctoral Dissertation, Universitat Hamburg Fachbereich Chemie; Hamburg; 1975).   An English translation of Westendorf’s doctoral disser, is available on the web at  http://www.dartmouth.edu/~rmasters/slub.htm .  (to access, follow instructions at the end of the “forward” to the translation by Jakob von Moltke).   See also Knappwost A and Westendorf J; "On the Inhibition of Acetylcholinesterase by Fluoride"; Naturwissenschaft 61; 1974; 274-275 and "Inhibition of Cholinesterase by Fluorocomplexes of Silicon and Iron"; Ibid p 275.   Although this research seems to have escaped the attention of US health authorities, it provides important evidence that SiF treated water is not “just like” NaF treated water that has not been taken into account by either critics or supporters of water fluoridation.

[xxix] Urbansky, ET and Schock, MR. “Can fluoridation effect lead(II) in potable water?  Hexafluorosilicate and fluoride equilibria in aqueous solution,” International Review of Environmental Studies, 57 (2000) 597-637,  available on the web at http://fluoride.oralhealth.org/papers/urbansky.pdf


[xxx] National Institutes of Health, Transcript of Proceedings, Surgeon General’s (Koop) Ad Hoc Committee on ‘Non-Dental Health Effects of Fluoride,” Day I (April 18, 1983), Bethesda, MD: Stenotech, Inc., 1983), I, esp. 132-139 (Dr. Frank Smith’s description of the experimental studies of “fluoride absorption” and “fluoride in blood” without reference to specific chemicals to which research animals were exposed.)

[xxxi] U. S. Department of Health and Human Services, Oral Health in America: A Report of the Surgeon General (Rockville, MD: U.S. Department of Health and Human Services, 2000);

[xxxii] APHA Resolution LB-00-7 (2000): “Support the Framework for Action on Oral health in America: A Report of the Surgeon General,” American Journal of Public Health 91 (20001), 520.

[xxxiii] Fluoride Recommendations Work Group, “Recommendations for Using Fluoride to Prevent and Control Dental Caries in the United States, “MMWR(August 17, 2001) 50 (RR14): 1-42.  URL: http:www.cdc.gov/mmwr/.  See also CDC Press Release: “CDC releases new guidelines of fluoride use to prevent tooth decay,” August 16, 2001.  URL:http://www.cdc.gov/od/oc/media/pressrel/4r010817.htm  


[xxxiv] Crosby NT.  (1969). Equilibria of fluorosilicate:  Solutions with special reference to the fluoridation of public water supplies.  Journal of Applied Chemistry. 19:100-2.  For a detailed critique of Crosby’s methodology, including his selective use of rounding to whole numbers to hide incomplete dissociation, see Myron J. Coplan’s correspondence with the APHA, available at the website:
http://www.dartmouth.edu/~rmasters/ahabs.htm.

[xxxv] Center for Disease Control, Fluoridation Census 1992 (Atlanta: Department of Health and Human Services, 1992).

[xxxvi] For a fuller analysis of this topic, from which the following section is adapted, see Myron J. Coplan, Reply to APHA Oral Health Section Objections to Proposed APHA Resolution (July 2000).

[xxxvii] McClure  FJ; “A Review of Fluorine and its Physiological Effects”; Physiological Reviews vol XIII, No. 3, July 1933, pp 277-300)

[xxxviii] Ibid., p. 291. It should be noted that the fluoride level in this experiment was far lower than 1 ppm

[xxxix] Kick CH, Bethke RM, Edgington BH, Wilder OHM, Record PR, et al. 1935.  Fluorine in animal nutrition. Ohio Agricultural Experiment Station Bulletin 558:1-77.

[xli] Coradin T and Livage J; “Effect of some amino acids and peptides on silicic acid polymerization;” Colloids Surf B Biointerfaces; 2001 Aug; 21(4):329-336

[xlii] Allderdice PW et al; “The cloned butyrylcholinesterase (BCHE) gene maps to a single chromosome site, 3q26”; Genomics 1991 Oct;11(2):452-4.

[xliii] C. Lejus, et al; “Cholinesterases”; Ann Fr Anesth Reanim 1998;17(9):1122-35.

[xliv] P. G. Layer,  “Nonclassical roles of cholinesterases in the embryonic brain and possible links to Alzheimer disease”; Alzheimer Dis Assoc Disord 1995;9 Suppl 2:29-36).

[xlv] L. Margolis L; Nature 264, 620, 1976, cited in Iler Ralph K.; “The Chemistry of Silica; Solubility, Polymerization, Colloid and Surface Properties, and Biochemistry”; John Wiley & Sons; New York, 1979.

[xlvi] Ibid., p. 764.

[xlvii] Mohammed B. Abou-Donia,  et al., “Locomotor and Sensorimotor Performance Deficit in Rats following Exposure to Pyridostigmine Bromide, DEET, and Permethrin, Alone and in Combination,” Toxicological Sciences, 60 (2001) 305-314.; M. B. Abou-Donia, et al., “Effects of Daily Dermal Application of DEET and Permethrin, Alone and in Combination, on Sensorimotor Performance, Blood-Brain Barrier, and Blood-Testis Barrier in Rats,” Journal of Toxicology and Environmental Health,  Part A 62 (2001) 523-541.

[xlviii] See references in notes above.

[xlix] By the same token, though McClure was interested in amyulase inhibition by fluorides, there is no indication that he was aware of fluoride inhibition of AchE. F. J. McClure : “The Effect of Fluorides on Salivary Amylase”: Pub Heath Rep. 54; 2165-2171;1939.

[l] Knappwost A and Westendorf J; “On the Inhibition of Acetylcholinesterase by Fluoride,” Naturwissenschaft 61; 1974; 274-275 and “Inhibition of Cholinesterase by Fluorocomplexes of Silicon and Iron”; Ibid p 275).

[li] We thank Adrian Bailey and James Sargent for making available to us this data, for which they previously showed the role of lead residues from industrial activities:   A. J. Bailey, J. D. Sargent, D. C. Goodman, J. Freeman and M. J. Brown "Poisoned Landscapes: The Epidemiology of Environmental Lead Exposure in Massachusetts Children 1990-1991" Social Science Med. 39, 757-776(1994).

[lii] Roger D. Masters and Myron Coplan, “Water Treatment with Silicofluorides and Lead Toxicity,” International Journal of Environmental Studies, 56 (1999) 435-490.

[liii] R. D. Masters, M. J. Coplan, B. T. Hone, and J. E. Dykes, “Association of Silicofluoride Treated Water with Elevated Blood Lead,” Neurotoxicology, 21 (2000), 1091-1100.

[liv] R. D. Masters, M. J. Coplan, B. Hone, and J. Dykes, “Heavy Metal Toxicity, Cognitive Development, and Behavior,” Poster Session, 17th Annual Neurotoxicology Conference, Little Rock, ARK, Oct. 17-20, 1999). 

[lv] Masters and Coplan, “Water Treatment with Silicofluorides and Lead Toxicity,”  (note 51), pp. 440-441.  .  A footnote added to this passage indicates: “Towns using sodium fluorosilicate reported lower first draw water lead values (11.7 ppb) than unfluoridated towns (21.2 ppb) or towns using sodium fluoride (17.5 ppb); communities using fluosilicic acid had significantly higher levels of lead than in others (39.3 ppb).   Although the difference between usage of fluosilicic acid and all other treatment conditions is highly significant (p < .0001, DF 3, 223, F 9.32), differences in lead in first draw water cannot account for the fact that levels of children's blood lead are comparable in towns using sodium silicofluoride and fluosilicic acid.  In any event, there is one order of magnitude difference between lead levels reported in water supplies (in parts per billion or10-9) and measures of lead uptake in blood (micrograms per deciliter are equivalent to parts per one hundred million or 10-8).  (Ibid., note 22).

[lvi] Masters and Coplan, “Water Treatment with Silicofluorides and Lead Toxicity,” (n. 51), pp. 443-444.   It should be noted that the increment in average children’s blood lead from use of sodium fluoride (compared to unfluoridated water) is relatively small (0.14 µg/dL) if lead levels in 90th % first draw water are under 15ppb; if lead levels in water are above 15 ppb, children’s blood lead levels are actually 0.28 µg/dL lower where sodium fluoride is used than where water is not fluoridated.  In contrast, where lead in the water is above 15ppb, the increment compared to non-fluoridated communities is 1.09 µg/dL for the 25 communities using fluosilicic acid and 2.2 µg/dL in the one community using sodium silicofluoride.    Put another way, comparing the effect of fluoridating water with silicofluorides on uptake of lead above 15ppb in the public water supply rather than below that level is roughly three or four times worse if the chemical agent is a silicofluoride rather than sodium fluoride (Ibid., Table II, p. 443).  Analysis of variance shows that this effect, measured as the interaction between silicofluorides and lead levels in water over 15ppb is statistically significant: p = .0422; F = 4.18 (ibid., Figure 1, p. 444).

[lvii] Masters, Coplan, Hone, and Dykes, “Association of Silicofluoride Treated Water with Elevated Blood Lead,” (note 37), p. 1093.

[lviii] Masters, Coplan and Hone, 1999 (note and in preparation).

[lix]Masters and Coplan, “Water Treatment with Silicofluorides and Lead Toxicity,”  (1999), p. 443.##  .  Controlling for other sources of lead, silicofluoride usage remain significant, which (a  footnote adds) “is all the more impressive because multiple regression reveals that percentage of housing built before 1940 is a significant predictor of which towns use silicofluorides (controlling for population density, % vacant housing, per capita income,  racial composition, and other demographic variables).”
#
[lx] Masters,  Coplan, Hone, and Dykes, “Association of Silicofluoride Treated Water with Elevated Blood Lead,” (note 52),  Figures 1 and 2 (p. 1095).
##
[lxi] See references in notes – and ---.

[lxii] Masters, et al., “Association of SilicofluorideTreated Water With with Elevated Blood Lead Levels,” Figure 4.

[lxiii] The American Journal of Public Health issue in January 2002 had two articles germaine to this issue.  On prejudices and distrimination in the delivery of dental health care to poor minority children, see Mofidi, Mahyar; Rozier, R. Gary, and King, Rebecca S., “Problems with Access to Dental Care for Medicaid-Insured Children: What Caregivers Think,” American Journal of Public Health, 92 (2002) 53-58.  For the serious epidemic of dental health among Blacks in Harlem, where water is treated with silicofluorides, see Zabos, Georgina P.; Northridge, Mary E.; Ro, Marguerite Jul., Trinh, Chau; Vaughan, Roger; Howard, Joyce Moon, Lamster, Ira; Bassett, Mary T; and Cohall, Alwyn T., “Lack of Oral Health Care for Adults in Harlem: A Hidden Crisis,” American Journal of Public Health, 92 (2002) 49-52

[lxiv] In addition to the sources cited in notes – to ---, for a recent report see Paul B. Stretesky and Michael J. Lynch, “The Relation Between Lead Exposure and Homicide,” Archives of Pediatric and Adolescent Medicine, 155 (2001) 579-582.

[lxv] Carmona GN, Jufer RA, Goldberg SR, Gorelick DA,
Greig NH, Yu QS, Cone EJ, Schindler CW , “Butyrylcholinesterase accelerates cocaine metabolism: in vitro and in vivo effects in nonhuman primates and humans,” 
Drug Metab Dispos 28 (2000): 367-371.  The entire Abstract of this study  is worth citing: “Butyrylcholinesterase (BChE) is known to metabolize cocaine in humans. In the
present study, three different experiments were performed to determine
whether the addition of horse serum-derived BChE would accelerate the
metabolism of cocaine. In the first experiment, the addition of BChE to
squirrel monkey plasma in vitro reduced the half-life of cocaine by over 80%,
decreased the production of the metabolic product benzoylecgonine, and
increased ecgonine methyl ester formation. The effect of BChE on cocaine
metabolism was reversed by a specific BChE inhibitor. In the second, in vivo,
experiment, exogenously administered BChE reduced peak cocaine concentrations
when given to anesthetized squirrel monkeys. Finally, incubation of cocaine
with added BChE in human plasma in vitro resulted in a decrease in cocaine
half-life similar to that observed with squirrel monkey plasma. The magnitude
of the decrease in cocaine half-life was proportional to the amount of added
BChE. Together, these results indicate that exogenously administered BChE can
accelerate cocaine metabolism in such a way as to potentially lessen the
behavioral and toxic effects of cocaine. Therefore, BChE may be useful as a
treatment for cocaine addiction and toxicity.”

[lxv] Masters and Coplan, "A dynamic, multifactorial model of alcohol, drug abuse, and
crime: linking neuroscience and behavior to toxicology,” Table 6 (p. 616).

[lxvii] Ibid., Tables 3 and 6 (p. 608 & 616).

[lxvii] Georges Graeub, The Petkau Effect (New York: Four Walls Four Windows, 1994).


































APPENDIX
Myron J. Coplan

Although silicofluorides (SiFs), principally fluosilicic acid (FSA), have never been tested for health safety as water fluoridating agents, they are used to fluoridate 91% of the municipal water intended for human consumption in the United States.   Evidence published in peer-reviewed journals indicates that chronic ingestion of SiF-treated water is a cause of elevated blood lead in children. This evidence has been known by the EPA, CDC, and NIEHS since 1999, but they have disputed it with theoretical arguments and poor statistics.

Independent, new research has provided an explanation for the elevated blood lead. Unexpected amounts of lead are extracted from brass plumbing fixtures by water in which FSA is combined with chlorine or chloramine disinfectants. Ingesting such water or foods made with same will increase blood lead in children causing cognitive impairment and suppressed impulse control.

Moreover elevated blood lead has been unequivocally proven to damage tooth enamel integrity and increase susceptibility to caries. Dental fluorosis, considered “only cosmetic” by fluoridation proponents, has also been found to be more severe where silicon accompanies fluoride in naturally fluoridated areas. Elevated blood lead also impacts adults and particularly Black males, who are known to be more susceptible to hypertension and kidney problems from elevated blood lead.

Apart from blood lead health and behavioral issues with children and adults across all races, a heretofore unacknowledged 1975 German PhD thesis provides evidence that SiF-treated water is likely to disrupt enzyme functions with consequent additional adverse health and behavioral effects. FBI violent crime statistics also correlates with exposure to SiF-treated water, probably due to bio-mechanisms driven by lead intoxication and/or acetyl-cholinesterase inhibition.

In addition to any of the above, compelling evidence reported in a Harvard PhD thesis showed fluoridated water to be strongly associated with osteosarcoma. This thesis
has precipitated a controversy in which a Harvard professor, a dentist and fluoridation advocate, has allegedly tried to suppress disclosure of the findings of the thesis he supervised and approved in 2001.

                                         II. Demonstrable Supporting Facts

(1) Fluoride chemicals are only effective in preventing tooth decay when in contact with the outer surface of tooth enamel. Ingesting fluoride chemicals to prevent tooth decay is neither necessary nor without adverse side effects on health.

(2) The notion that any form of ingested “fluoride” chemical is like any other, as
regards health effects when ingested, is naive or disingenuous. Thus, to declare that “fluoride is fluoride is fluoride” bespeaks irresponsibility whether that catch phrase comes from one side of the fluoridation debate or the other.

(3) In 1945, sodium fluoride (NaF) was the first agent used to deliver one part per million of fluoride ion in drinking water with at least some primitive tests on animals for health safety. In 1947, FSA was substituted for NaF as a cheaper source of fluoride without any such testing. With savings that amounted to 4 cents per year per community resident, the US PHS endorsed the switch from NaF to SiF in 1950 because rat teeth took up an equal amount of fluoride from each and rats grew at the same rate. In passing, the Public Health Report author (FJ McClure) mentions that significantly more of any excess fluoride was eliminated in the urine of SiF exposed rats than in the urine of NaF exposed rats. Thus fluoride levels in the bloodstream also had to be higher in the rats ingesting SiF-treated water, with consequent more intense exposure of soft tissues to fluoride.

(4) A 1999 letter from EPA Asst. Administrator Charles Fox to Congressman Ken Calvert admits the EPA had no evidence of any animal tests of SiF-treated water even though almost all US fluoridated water is treated with FSA.

(5) Data for over 400,000 children, 250,000 in Massachusetts, 150,000 in New York State, and 6,000 in the NHANES III child sample, consistently showed a statistically significant association between elevated blood lead and living in a community with SiF treated municipal water (Masters et al 2000, and Masters and Coplan 1999).

Subsequent to these publications, in 2002 the National Toxicology program nominated these compounds for study on the grounds that SiF “toxicology” was not known.  As of August 2007, however, there are no reports of such a study – or even of the designation of a team to research the possibility of toxic effects of SiF.


(6) The University of North Carolina Environmental Quality Institute (EQI) has found that lead-bearing brass plumbing in the absence of any other source such as lead pipes is corroded by SiF treated water to such an extent that it should be considered as a serious source of ingested lead.

(7)  In 1945, 10-15 % of children drinking naturally fluoridated water exhibited dental fluorosis, mostly mild. In 1993 a National Research Council (NRC) report noted that up to 51% of children drinking SiF-treated water exhibited dental fluorosis with 14% moderate-to-severe and some severe. The idea that fluorosis is merely “cosmetic” was challenged in a
2006 NRC report citing fluorosis as a “toxic effect that is consistent with prevailing risk assessment definitions of adverse health effects.” It also noted that drinking water is a major source of the fluoride causing the fluorosis.

(8) It is now established that dental fluorosis is due to inhibition of the enzymes that remove proteins responsible for tooth enamel formation

(9) Enzyme inhibition by SiF was also the subject of a German PhD thesis which focused on inhibiting acetylcholinesterase (AChE).  AChE plays a vital role in proper functioning of cholinergic neural systems responsible for both voluntary and involuntary muscular processes. For instance, AChE quenches acetylcholine (ACh) activity after it has transmitted excitatory signals across a synaptic gap to a muscle end-plate. If that quenching is totally suppressed, muscle excitation would be prolonged, and a spasm would occur that can be fatal (which is a short-hand description of how nerve gas works).

(10) An equally important example of enzyme inhibition concerns “serum cholinesterase” whose function includes scavenging blood-borne toxins that might otherwise interfere with the normal healthy interactions of ACh and AChE.

(11) Apart from direct adverse health problem from ingested SiFs, it should be noted that SiF treated water is a potential source of low level internal radiation from contaminating radio-nuclides; this is a possible cause of osteosarcoma, which has been observed more frequently where water is treated with SiF.


(12) The CDC has funded a former CDC employee to carry out a statistical study to refute the SiF/blood lead link. Ironically, rather than proving that there is none, even after employing unwarranted statistical methods, this study actually confirmed that there is a 70% greater risk of elevated blood lead for children receiving SiF treated water due to increased absorption of environmental lead to which they are exposed.


(13) A dentist and vigorous proponent of fluoridation recently completed a study titled “Association Between Race/Ethnicity and Early Childhood Caries in California Pre-School Children.”http://www.nidcr.nih.gov/NewsAndReports/ReportsPresentation/ DirectorsReportCouncil092003.htm). It concluded:

     “... water fluoridation status of the children's area of residence did not have
      a significant effect on ECC and may be indicative of a lack of water intake.”

(14) The ineffectiveness of fluoridated water in the populations studied should not have been a surprise. Similar results were reported by the Public Health Service in 1992 but they weren’t blamed on not drinking enough fluoridated water: (Barnes GP, et al; “Ethnicity, location, age, and fluoridation factors in baby bottle tooth decay and caries prevalence of Head Start children”; Public Health Rep. 1992 Mar-Apr;107(2):167-73).

(15) Finally, this synopsis would be incomplete without comment on research conducted by the Forsyth Dental Center in the late 1970s (Glass RL; Caries Res. 1981;15(5):445-50) which concluded that tooth decay had declined in two non-fluoridated Boston suburbs at the same rate as in fluoridated Boston. Similar results were mentioned in a 1980 Journal of Dental Research Abstract authored by other Forsyth staff members (PF DePaola, P Soparkar,  M Allukian, R DeVelis, and M Resker) titled “Changes in Caries Prevalence of Massachusetts Children Over Thirty Years.” A key phrase in that abstract reads as follows:

   “A comparison of the present preliminary findings to those of nearly 30 years
     ago suggest a decline in caries prevalence of 40-50%. The decline cannot be
     attributed to water fluoridation and seems too large to be explained trivially,
     e.g. because of differences in diagnostic standards.”     

Forsyth management convened the “First International Conference on the Declining Prevalence of Dental Caries” to be held at Forsyth June 25-26, 1982. The conference proceedings eventually comprised an entire Special Issue of the Journal of Dental Research published in November 1982. Over a dozen countries provided data confirming a decline in tooth decay without benefit of exposure to fluoridated drinking water. In summarizing these findings a major member of the Forsyth management made this remarkable statement:  
     “In summary, we have presented some data here today which make us
      reasonably certain that dental caries has declined in Massachusetts, and
      some additional data which make us at least suspect that this decline is part
      of a wider pattern of national and international scope. We have also commented
      upon some factors to consider in relation to declining caries rates.

      When dealing with these findings one is faced with a dilemma. On the one
      hand, it is obviously important to develop the earliest possible awareness of a
      significant downward shift in caries prevalence because of the profound
      implications of such a phenomenon and, indeed, we view this as the justification
      for this report. On the other hand, if we judge erroneously or prematurely that
      such a shift has occurred, or if we misjudge the magnitude of the shift, there
      is the danger of fostering the belief that dental caries is no longer a serious
      problem. And, even if we make no such mistake, there is still something to
      be worried about. Recall the European data, for example, which shows declines
      in caries which are occurring without fluoridation. This could easily become
      ammunition for the antifluoridationists despite the fact that the data do not           
      diminish the overwhelming importance of fluoridation by one iota.”                   
        
 
The contradiction between the last two sentences is easily explained and illustrates the gap between recent scientific findings and typical political statements on the issue.


[lxviii] Georges Graeub, The Petkau Effect (New York: Four Walls Four Windows, 1994).
* Research on silicofluoride toxicity described in this paper has been conducted in collaboration with Myron J. Coplan (Intellequity Consulting, Natick, MA), whose expertise in chemical engineering and the history of fluoridation are the basis of statements on the chemistry if SiF in this and our joint publications.  Former Vice President and General Manager of the Albany International Co. Membrane Development Venture,  Mr. Coplan’s experience includes direct professional work with silicofluorides as well as numerous areas of public policy (see his statement at <http://www.thehealthvine.net/index.php?option=com_content&view=article&id=81&Itemid=121>.  Our collaboration reflects the extent to which research on many issues linking environmental toxicity, brain chemistry, and public policy can no longer be conducted by a solitary researcher.  Errors in the restatement below are entirely my responsibility, and reflect the need for treating interdisciplinary research as an on-going dialogue in which political scientists have an obligation to


[1] Gottschalk L, Rebello T, Buchsbaum MS, Tucker HG,  Hodges HL. 1991. Abnormalities in trace elements as indicators of aberrant behavior.Comprehensive Psychiatry  342:229-37


[1] See the letter from Benjamin Franklin to Benjamin Vaughan “on the bad Effects of Lead taken inwardly” (31 July 1786) in Lemay, ed.,
Complete Writings of Benjamin Franklin  (New York: Library of America, 1987), pp. 1163-1166.

[1] Herbert Needleman, ed.,  Human Lead Exposure  (Boca Raton, FL: CRC Press, 1989).

[1] Bryce-Smith D.  1983.  Lead induced disorder of mentation in children.Nutrition and Health.  1:179-94.

[1] Debbie Cory-Slechta, “Relationships between Lead Induced Learning Impairments and Change in Dopaminergic, Cholinergic, Glutamatergic Neurotransmitter System Functioning,” Annual Review of Pharm. Toxic. 35: 3337-395 (1995),

[1] Needleman HL, Gatsonis B. 1991.  Meta-analysis of 24 studies of learning disabilities due to lead poisoning. JAMA  265:673-78

[1] Bellinger D, et al.  1994.  Pre-and postnatal lead exposure and behavior problems in school-aged children. Environmental Research.  66:12-30

[1]Needleman HL.  1999.  Environmental neurotoxins and attention deficit disorder, Presentation at Conference on Environmental Neurotoxins and Developmental Disability, N. Y. Academy of Medicine, New York, May 24-25

[1] Tuthill RW. 1996.  Hair lead levels related to children's classroom attention-deficit behavior. Archives of Environmental Health.  51:214-20.

[1] Minder B, Das-Smaal EA, Brand, EF,  Orlebeke JM, Jacob F.  1994.  Exposure to lead and specific attentional problems in schoolchildren. Journal of Learning Disabilities. 27:393-98.

[1] Kahn CA, Kelly, PC, Walker WO. 1995.  Lead screening in children with attention deficit hyperactivity disorder and developmental delay. Clinical Pediatrics. 34:498-501.

[1] Cook E.H, et al.  1995.  Association of attention deficit disorder and the dopamine transporter gene.  American Journal of Human Genetics, 56,

[1] Wollan M. 1968.  Controlling the potential hazards of Government-sponsored technology, Geo. Washington Law Review.  36: 1105-20.

[1] For the example to be discussed below, see the web-sitehttp://www.dartmouth.edu/~rmasters/ahabs.htm.

[1]Masters, R,, Hone, B, and Doshi, A.   (1998).  “Environmental Pollution, Neurotoxicity, and Criminal Violence,” in J. Rose, ed., Environmental Toxicology: Current Developments (London: Gordon and Breach, 1998), pp. 13-48.

[1] Kitman Jamie Lee; “The Secret History of Lead. (use of leaded gasoline)”;  The Nation, March 20, 2000 v270.   This article includes especially revealing on the origins of tetrethyl lead usage with knowledge of its toxicity.

[1] Masters, Roger D., “Biology and Politics: Linking Nature and Nurture,” in Nelson Polsby, ed., Annual Review of Political Science, Vol. 4 (Palo Alto, CA: Annual Reviews, 2001), pp. 353-356 and esp. Figure 2, p. 356.

[1] E. Paulesu, J.-F. Démonet, F. Fazio, E. McCrory, V. Chanoine, N. Brunswick, S.F. Cappa, G. Cossu, M. Habib, C.D.Frith, U. Frith, “Dyslexia: Cultural Diversity and Biological Unity,” Science 291 (17 March 2001), 2165-2167.

[1] Rudolf N. Cardinal, David R. Pennicott, C. Lakmati Sugathapala, Trevor W. Robbins, Bary J. Everitt.  2001.  “Impulsive Choice Induced in Rats by Lesions of the Nucleus Accumbens Core,” Science 292 (29 June 2001) 2499-2501.

[1] See references cited in notes 6 and 7 above.

[1] Brockel BA, Cory-Slechta DA. 1998.   Lead, attention, and impulsive behavior:  changes in a fixed-ratio waiting-for-reward paradigm. Pharmacology Biochemistry and Behavior.  60:545-52.

[1] Sydney Walker, The Hyperactivity Hoax: How to Stop Drugging Your Child and Find Real Medical Help.    (New York: St Martin’s Press, 1998).

[1] See Myron J. Coplan and Roger Masters, Should Silicofluoride Be Used To Fluoridate Municipal Water? Submitted to Congressman Kenneth Calvert, Chair of Subcommittee on Energy and the Environment, Committee on Science, U.S. House of Representatives. April, 2000; idem, Response to EPA Staff Unsupportable Dismissal of Evidence of Adverse Silicofluoride Health Effects. Report to EPA, June 12, 2000; idem, Scientific Misconduct at EPA.  Report to Hon Kenneth Calvert, Chair of Subcommittee on Energy and the Environment, Committee on Science, US House of Representatives, September 25, 2000.

[1] “To answer your first question on whether we have in our possession empirical scientific data on the effects of fluosilicic acid or sodium silicofluoride on health and behavior, our answer is no…. We have contacted our colleagues at NHEERL and they report that with the exception of some acute toxicity data, they were unable to find any information on the effects of silicofluorides on health and behavior.”   Robert C. Thurnau [Chief, Treatment Technology Evaluation Branch, Water Supply and Water Resources Division, U.S. EPA National Risk Management Research Laboratory, Cincinatti, OH] to Roger Masters, Nov. 16, 2000.

[1] Andrew Rymer.  The (Political) Science of Fluoridating Public Water Supplies.    Senior Honors Thesis, Dartmouth College, Hanover, NH, 2000; pp. 112 + 14 primary documents

[1] E.g., in 1951, a principal proponent of extending water fluoridation – Francis Bull – explicitly told a dental convention never to mention the chemicals to be used.  This practice has persisted.  For instance, in the recent report on Oral Health in the US – 2000, Surgeon General Satcher speaks of “fluoridation” without mentioning the chemicals used.    With few exceptions, critics of water fluoridation have long addressed the issue in similar terms.

[1] McClure, 1950. Years later, several experiments were published that purported to confirm this prediction, but the studies used an ion specific electrode method that required conditions unlike those of a water treatment facility and the reported results rounded figures to the nearest whole number (thereby hiding evidence of incomplete dissociation).

[1] Westendorf  Johannes.  1975.  "Die Kinetik der Acetylcholinesterase hemmung und Die Beeinflussung der  Permeabilitat von Erythrozytenmembranen durch Fluorid und Flurocomplex-Jonen"; Doctoral Dissertation, Universitat Hamburg Fachbereich Chemie; Hamburg; 1975).   An English translation of Westendorf’s doctoral disser, is available on the web at  http://www.dartmouth.edu/~rmasters/slub.htm .  (to access, follow instructions at the end of the “forward” to the translation by Jakob von Moltke).   See also Knappwost A and Westendorf J; "On the Inhibition of Acetylcholinesterase by Fluoride"; Naturwissenschaft 61; 1974; 274-275 and "Inhibition of Cholinesterase by Fluorocomplexes of Silicon and Iron"; Ibid p 275.   Although this research seems to have escaped the attention of US health authorities, it provides important evidence that SiF treated water is not “just like” NaF treated water that has not been taken into account by either critics or supporters of water fluoridation.

[1] Urbansky, ET and Schock, MR. “Can fluoridation effect lead(II) in potable water?  Hexafluorosilicate and fluoride equilibria in aqueous solution,” International Review of Environmental Studies, 57 (2000) 597-637,  available on the web at http://fluoride.oralhealth.org/papers/urbansky.pdf


[1] National Institutes of Health, Transcript of Proceedings, Surgeon General’s (Koop) Ad Hoc Committee on ‘Non-Dental Health Effects of Fluoride,” Day I (April 18, 1983), Bethesda, MD: Stenotech, Inc., 1983), I, esp. 132-139 (Dr. Frank Smith’s description of the experimental studies of “fluoride absorption” and “fluoride in blood” without reference to specific chemicals to which research animals were exposed.)

[1] U. S. Department of Health and Human Services, Oral Health in America: A Report of the Surgeon General (Rockville, MD: U.S. Department of Health and Human Services, 2000);

[1] APHA Resolution LB-00-7 (2000): “Support the Framework for Action on Oral health in America: A Report of the Surgeon General,” American Journal of Public Health 91 (20001), 520.

[1] Fluoride Recommendations Work Group, “Recommendations for Using Fluoride to Prevent and Control Dental Caries in the United States, “MMWR(August 17, 2001) 50 (RR14): 1-42.  URL: http:www.cdc.gov/mmwr/.  See also CDC Press Release: “CDC releases new guidelines of fluoride use to prevent tooth decay,” August 16, 2001.  URL:http://www.cdc.gov/od/oc/media/pressrel/4r010817.htm  


[1] Crosby NT.  (1969). Equilibria of fluorosilicate:  Solutions with special reference to the fluoridation of public water supplies.  Journal of Applied Chemistry. 19:100-2.  For a detailed critique of Crosby’s methodology, including his selective use of rounding to whole numbers to hide incomplete dissociation, see Myron J. Coplan’s correspondence with the APHA, available at the website:
http://www.dartmouth.edu/~rmasters/ahabs.htm.

[1] Center for Disease Control, Fluoridation Census 1992 (Atlanta: Department of Health and Human Services, 1992).

[1] For a fuller analysis of this topic, from which the following section is adapted, see Myron J. Coplan, Reply to APHA Oral Health Section Objections to Proposed APHA Resolution (July 2000).

[1] McClure  FJ; “A Review of Fluorine and its Physiological Effects”; Physiological Reviews vol XIII, No. 3, July 1933, pp 277-300)

[1] Ibid., p. 291. It should be noted that the fluoride level in this experiment was far lower than 1 ppm

[1] Kick CH, Bethke RM, Edgington BH, Wilder OHM, Record PR, et al. 1935.  Fluorine in animal nutrition. Ohio Agricultural Experiment Station Bulletin 558:1-77.

[1]
[1] Coradin T and Livage J; “Effect of some amino acids and peptides on silicic acid polymerization;” Colloids Surf B Biointerfaces; 2001 Aug; 21(4):329-336

[1] Allderdice PW et al; “The cloned butyrylcholinesterase (BCHE) gene maps to a single chromosome site, 3q26”; Genomics 1991 Oct;11(2):452-4.

[1] C. Lejus, et al; “Cholinesterases”; Ann Fr Anesth Reanim 1998;17(9):1122-35.

[1] P. G. Layer,  “Nonclassical roles of cholinesterases in the embryonic brain and possible links to Alzheimer disease”; Alzheimer Dis Assoc Disord 1995;9 Suppl 2:29-36).

[1] L. Margolis L; Nature 264, 620, 1976, cited in Iler Ralph K.; “The Chemistry of Silica; Solubility, Polymerization, Colloid and Surface Properties, and Biochemistry”; John Wiley & Sons; New York, 1979.

[1] Ibid., p. 764.

[1] Mohammed B. Abou-Donia,  et al., “Locomotor and Sensorimotor Performance Deficit in Rats following Exposure to Pyridostigmine Bromide, DEET, and Permethrin, Alone and in Combination,” Toxicological Sciences, 60 (2001) 305-314.; M. B. Abou-Donia, et al., “Effects of Daily Dermal Application of DEET and Permethrin, Alone and in Combination, on Sensorimotor Performance, Blood-Brain Barrier, and Blood-Testis Barrier in Rats,” Journal of Toxicology and Environmental Health,  Part A 62 (2001) 523-541.

[1] See references in notes above.

[1] By the same token, though McClure was interested in amyulase inhibition by fluorides, there is no indication that he was aware of fluoride inhibition of AchE. F. J. McClure : “The Effect of Fluorides on Salivary Amylase”: Pub Heath Rep. 54; 2165-2171;1939.

[1] Knappwost A and Westendorf J; “On the Inhibition of Acetylcholinesterase by Fluoride,” Naturwissenschaft 61; 1974; 274-275 and “Inhibition of Cholinesterase by Fluorocomplexes of Silicon and Iron”; Ibid p 275).

[1] We thank Adrian Bailey and James Sargent for making available to us this data, for which they previously showed the role of lead residues from industrial activities:   A. J. Bailey, J. D. Sargent, D. C. Goodman, J. Freeman and M. J. Brown "Poisoned Landscapes: The Epidemiology of Environmental Lead Exposure in Massachusetts Children 1990-1991" Social Science Med. 39, 757-776(1994).

[1] Roger D. Masters and Myron Coplan, “Water Treatment with Silicofluorides and Lead Toxicity,” International Journal of Environmental Studies, 56 (1999) 435-490.

[1] R. D. Masters, M. J. Coplan, B. T. Hone, and J. E. Dykes, “Association of Silicofluoride Treated Water with Elevated Blood Lead,” Neurotoxicology, 21 (2000), 1091-1100.

[1] R. D. Masters, M. J. Coplan, B. Hone, and J. Dykes, “Heavy Metal Toxicity, Cognitive Development, and Behavior,” Poster Session, 17th Annual Neurotoxicology Conference, Little Rock, ARK, Oct. 17-20, 1999). 

[1] Masters and Coplan, “Water Treatment with Silicofluorides and Lead Toxicity,”  (note 51), pp. 440-441.  .  A footnote added to this passage indicates: “Towns using sodium fluorosilicate reported lower first draw water lead values (11.7 ppb) than unfluoridated towns (21.2 ppb) or towns using sodium fluoride (17.5 ppb); communities using fluosilicic acid had significantly higher levels of lead than in others (39.3 ppb).   Although the difference between usage of fluosilicic acid and all other treatment conditions is highly significant (p < .0001, DF 3, 223, F 9.32), differences in lead in first draw water cannot account for the fact that levels of children's blood lead are comparable in towns using sodium silicofluoride and fluosilicic acid.  In any event, there is one order of magnitude difference between lead levels reported in water supplies (in parts per billion or10-9) and measures of lead uptake in blood (micrograms per deciliter are equivalent to parts per one hundred million or 10-8).  (Ibid., note 22).

[1] Masters and Coplan, “Water Treatment with Silicofluorides and Lead Toxicity,” (n. 51), pp. 443-444.   It should be noted that the increment in average children’s blood lead from use of sodium fluoride (compared to unfluoridated water) is relatively small (0.14 µg/dL) if lead levels in 90th % first draw water are under 15ppb; if lead levels in water are above 15 ppb, children’s blood lead levels are actually 0.28 µg/dL lower where sodium fluoride is used than where water is not fluoridated.  In contrast, where lead in the water is above 15ppb, the increment compared to non-fluoridated communities is 1.09 µg/dL for the 25 communities using fluosilicic acid and 2.2 µg/dL in the one community using sodium silicofluoride.    Put another way, comparing the effect of fluoridating water with silicofluorides on uptake of lead above 15ppb in the public water supply rather than below that level is roughly three or four times worse if the chemical agent is a silicofluoride rather than sodium fluoride (Ibid., Table II, p. 443).  Analysis of variance shows that this effect, measured as the interaction between silicofluorides and lead levels in water over 15ppb is statistically significant: p = .0422; F = 4.18 (ibid., Figure 1, p. 444).

[1] Masters, Coplan, Hone, and Dykes, “Association of Silicofluoride Treated Water with Elevated Blood Lead,” (note 37), p. 1093.

[1] Masters, Coplan and Hone, 1999 (note and in preparation).

[1]Masters and Coplan, “Water Treatment with Silicofluorides and Lead Toxicity,”  (1999), p. 443.##  .  Controlling for other sources of lead, silicofluoride usage remain significant, which (a  footnote adds) “is all the more impressive because multiple regression reveals that percentage of housing built before 1940 is a significant predictor of which towns use silicofluorides (controlling for population density, % vacant housing, per capita income,  racial composition, and other demographic variables).”
#
[1] Masters,  Coplan, Hone, and Dykes, “Association of Silicofluoride Treated Water with Elevated Blood Lead,” (note 52),  Figures 1 and 2 (p. 1095).
##
[1] See references in notes – and ---.

[1] Masters, et al., “Association of SilicofluorideTreated Water With with Elevated Blood Lead Levels,” Figure 4.

[1] The American Journal of Public Health issue in January 2002 had two articles germaine to this issue.  On prejudices and distrimination in the delivery of dental health care to poor minority children, see Mofidi, Mahyar; Rozier, R. Gary, and King, Rebecca S., “Problems with Access to Dental Care for Medicaid-Insured Children: What Caregivers Think,” American Journal of Public Health, 92 (2002) 53-58.  For the serious epidemic of dental health among Blacks in Harlem, where water is treated with silicofluorides, see Zabos, Georgina P.; Northridge, Mary E.; Ro, Marguerite Jul., Trinh, Chau; Vaughan, Roger; Howard, Joyce Moon, Lamster, Ira; Bassett, Mary T; and Cohall, Alwyn T., “Lack of Oral Health Care for Adults in Harlem: A Hidden Crisis,” American Journal of Public Health, 92 (2002) 49-52

[1] In addition to the sources cited in notes – to ---, for a recent report see Paul B. Stretesky and Michael J. Lynch, “The Relation Between Lead Exposure and Homicide,” Archives of Pediatric and Adolescent Medicine, 155 (2001) 579-582.

[1] Carmona GN, Jufer RA, Goldberg SR, Gorelick DA,
Greig NH, Yu QS, Cone EJ, Schindler CW , “Butyrylcholinesterase accelerates cocaine metabolism: in vitro and in vivo effects in nonhuman primates and humans,” 
Drug Metab Dispos 28 (2000): 367-371.  The entire Abstract of this study  is worth citing: “Butyrylcholinesterase (BChE) is known to metabolize cocaine in humans. In the
present study, three different experiments were performed to determine
whether the addition of horse serum-derived BChE would accelerate the
metabolism of cocaine. In the first experiment, the addition of BChE to
squirrel monkey plasma in vitro reduced the half-life of cocaine by over 80%,
decreased the production of the metabolic product benzoylecgonine, and
increased ecgonine methyl ester formation. The effect of BChE on cocaine
metabolism was reversed by a specific BChE inhibitor. In the second, in vivo,
experiment, exogenously administered BChE reduced peak cocaine concentrations
when given to anesthetized squirrel monkeys. Finally, incubation of cocaine
with added BChE in human plasma in vitro resulted in a decrease in cocaine
half-life similar to that observed with squirrel monkey plasma. The magnitude
of the decrease in cocaine half-life was proportional to the amount of added
BChE. Together, these results indicate that exogenously administered BChE can
accelerate cocaine metabolism in such a way as to potentially lessen the
behavioral and toxic effects of cocaine. Therefore, BChE may be useful as a
treatment for cocaine addiction and toxicity.”

[1] Masters and Coplan, "A dynamic, multifactorial model of alcohol, drug abuse, and
crime: linking neuroscience and behavior to toxicology,” Table 6 (p. 616).

[1] Ibid., Tables 3 and 6 (p. 608 & 616).

[1] Georges Graeub, The Petkau Effect (New York: Four Walls Four Windows, 1994). 

No comments:

Post a Comment