Why is the Early-Postnatal Period a Time of Special Concern regarding Effects of Developmental Toxins?
EPA researchers have stated, “Neurotoxic effects of a number of environmental agents have been demonstrated in various studies, with critical windows of vulnerability to these agents occurring both pre- and postnatally.” 1 Statements by the NIH, a commission of the U.S. National Academies, the U.S. Agency for Toxic Substances and Disease Registry (ATSDR) and academic experts also point to postnatal periods of vulnerability to toxins. (see Section 1, cont.) According to other EPA researchers, studies “have clearly demonstrated that when proliferation is actively occurring in a given region of the brain, it is vulnerable” to toxins;2 to see evidence that most proliferation in the brain is postnatal, see the brain growth charts below as well as the text above and below them. Formation of connections in the brain, vulnerable to toxins and strongly implicated in autism, is especially postnatal. (Much more on all of the above will be found in Section 1, cont.)
Section 2, intro.: The early-postnatal period is one of greatly increased exposures to neuro-developmental toxins, compared with prenatal exposures but also as compared with established safe doses. According to two experts on this topic (in line with other expert statements), "Significantly more (10 to 20 times) of a mother's body burden of persistent organohalogens is transferred to the infant via the milk than by the transplacental route."3 (Organohalogens include dioxins, PCBs, PBDEs, and organochlorine pesticides, all of which are neurodevelopmental toxins.) According to researchers contracted by the EPA, "a wealth of information" indicates that lactational transfer of maternal mercury during the first 15 days after birth is equal to about a third of the total transfer of mercury that takes place during gestation.3b Mercury concentrations in infants were found in an authoritative study to be three times as high in infants breastfed for one year as in bottle-fed infants, with compatible findings in another study.3c
Section 3, intro.: Scores of studies have found developmental harm associated with infants’ postnatal exposures to widespread environmental toxins; over 30 of those studies found less or no effects of prenatal exposures to those same toxins. See Section 3, cont.
A 2006 study in Toxicological Sciences, an Oxford Journal, confirms continuation of the brain’s vulnerable “growth spurt” during the first two years of life.(3a)
As stated by an EPA-contracted research group, "the brain is especially vulnerable (to metals) during the brain growth spurt."6 (According to the U.S. National Research Council, 83% of the human brain’s growth spurt is postnatal.6a) This especially postnatal vulnerability to metals should be seen together with awareness of human milk’s typically having four times the mercury concentration that is allowed in U.S. bottled water, and often higher.7 In a publication of the National Academies Press, in a section headed “Postnatal Effects of Neurotoxicants,” the authors state that “In humans, significant brain development and structural alteration occur until at least 4 to 6 years of age…. toxic exposures at a particular time would differentially affect the structures undergoing peak development.” 7a (See Section 4.a below about the postnatal peak development of the autism-linked cerebellum.) According to a publication of WHO, “Sensitivity to endocrine disruption is highest during tissue development.”7b (Mercury, dioxin, PCBs and PBDEs, all of which are substantially present in typical human milk, are all endocrine disruptors.)
4.a Especially great postnatal development and vulnerability of the cerebellum, with close links to autism: A 2009 study by eight scientists points out that, whereas neurons in the cortex develop mostly before birth, “Neurons in the cerebellum in contrast develop following birth;” (6a) and a 2010 study by a seven-scientist team says essentially the same thing.(6b) Also observe the cerebellum’s period of peak development in the charts above. Again, bear in mind that the various brain regions are especially vulnerable to toxins during their peak developmental periods.
A 2015 meta-analysis summarized, “There is ample evidence in the literature to suggest that cerebellar injury is the most consistent neuropathology finding among children with ASD.” (6e) Based on many earlier studies, a 2013 study also linked autism with problems of the cerebellum, based on “converging findings from human postmortem research, human neuroimaging studies, and animal models.”4 Several studies have found that this brain region was smaller in autistic than in non-autistic children.5 Given the numerous links that have been found between cerebellar deficits and autism, there is special significance in the cerebellum’s elevated postnatal vulnerability to toxins that results from its rapid, major postnatal growth. See just below about the greatly increased postnatal exposure of the developing brain to a toxin that is specifically known to damage the cerebellum.
Bearing in mind the increased vulnerability of the developing brain to metals during the (mainly postnatal) brain growth spurt, also remember the surge in a breastfed infant’s exposure to mercury, after birth (see Section 2 intro above and also see the text below Figure 2). Then note what the ATSDR says about the effects of mercury on the developing brain: “The predominant neuropathological feature (of mercury exposure) is degenerative changes in the cerebellum.”(6c) This distinct effect of mercury specifically on the cerebellum is very probably related to the predominantly postnatal time of the cerebellum’s growth(6a), (6b) combined with the fact that mercury is ingested by most infants in especially high doses during the early-postnatal period.
Summarizing the above, there are inter-connections between several factors here:
a) Dysfunction of the cerebellum has been closely linked with autism, in many studies;
b) the cerebellum’s development, and therefore its period of high vulnerability to toxins, is mostly postnatal;
c) the brain in general is especially vulnerable to metals postnatally (during the brain growth spurt);
d) there is a postnatal surge (via breastfeeding) in many infants’ exposures to developmental toxins, including mercury, a metal that is known to predominantly harm the cerebellum;
e) this widespread early-postnatal high exposure to developmental toxins occurs at the same time as the early-postnatal high vulnerability of the brain, especially the cerebellum;
f) the likely resulting damage to the cerebellum starts to take place during months before first signs of autism start appearing.
A web page of the NIH states that neonatal hypothyroidism, which it says can cause intellectual disability, can result from thyroid levels that are “only slightly low.” (5g) (“Neonatal” refers to the first four weeks after birth.) Bearing in mind the serious potential consequences of neonatal hypothyroidism, notice in the charts below the thyroid effects associated with postnatal mercury exposure at general U.S. background levels. This is from a study by a four-scientist team, analyzing a sample of 4,409 adults from the U.S. National Health and Nutrition Examination Survey (NHANES) 2007–2008.(5f)
Given the effect of background levels of mercury on adult thyroid levels as indicated above, consider the fact that, according to the ATSDR, “the results of a number of accidental (mercury) food poisonings indicate that children are more vulnerable” than adults to toxic effects of mercury.(5h) So infants, compared with adults, would be expected to have greater declines in thyroid levels if mercury exposure were to be equivalent to what applied to the above chart. But breastfed infants’ mercury exposures are likely to be much higher than normal adult exposures; a 1998 German study found that concentrations of mercury in breast milk of 85 lactating women at two months after birth had declined by an average of over 70% from their levels at time of birth.(5k) (That is compatible with the major increases in mercury in breastfed infants compared with formula-fed (see Section 2.intro.)) With such a large part of a grown person’s mercury burden rapidly passing to a small infant, it should reasonably be expected that the infant’s concentrations of that chemical would soon greatly exceed those of typical adults; that is especially true since absorption of ingested mercury has been found to be high during lactation, in an experiment with monkeys.(5m) Combining that increased exposure and absorption with the greater vulnerability of children to mercury’s effects, the resulting thyroid reduction in an infant would be expected to be significantly greater than what is shown in the above charts.
Also note that, according to a study by an EPA senior scientist, breastfed infants are exposed to dioxins in doses scores to hundreds of times higher than established safe levels;29 and dioxins, also, have been found to reduce thyroid hormones in human infants.44
Then remember the NIH statement that neonatal hypothyroidism (very possibly leading to mental disability) can result from thyroid levels that are “only slightly low.”
A 2004 study in the Journal of Neuroendocrinology, distinguishing between effects of prenatal versus postnatal low thyroid, found that “postnatal hypothyroidism exerts effects on cerebellar development.”5a (Remember from Section 4.a the close link between damage to the cerebellum and autism.) Those authors also observed, regarding other effects that could result from postnatal low thyroid, that ”hypothyroidism that extends even further in infancy is associated with poorer language, fine motor, auditory processing, attention and memory skills.” (emphasis added). Another study refers to the “striking reduction” in formation of connections of cerebellar neurons that results from hypothyroidism present perinatally (shortly before and after birth).5c Note that all of the above effects that could result from toxin-induced postnatal hypothyroidism, including effects on cerebellar development, are normal deficits of autism. Then remember (see below Figure 2, above, and accompanying text) the two toxins that have been found to reduce thyroid hormones postnatally, toxins to which infants are widely and heavily exposed by means of a voluntary process.
Section 5, preview: Effects of early-postnatal exposures to developmental toxins have been improperly overlooked.
Factors contributing to improper overlooking of effects: (a) Faulty assumptions about the duration of the brain’s period of development; (b) residual confounding in studies; (c) studies completed too soon to see long-term effects, or started too late to measure critical early exposures; (d) researchers’ biases, and distorted findings, as acknowledged at a very high level; (e) not testing exposed children for important impairments, including social competence, attention deficits, immune dysfunction, or long-term memory; and more. For details, see Section 5, cont. later.
Section 6: Certain widespread early-postnatal exposures to developmental toxins have been found in studies to directly correlate with autism, or to be logically linked with autism.
a) A study that investigated data from all 50 U.S. states and 51 U.S. counties found that "exclusive breast-feeding shows a direct epidemiological relationship to autism," and also, "the longer the duration of exclusive breast-feeding, the greater the correlation with autism."8 This has to do with a distinctly early-postnatal exposure; it could relate to possible nutritional deficiencies in the feeding (as suggested by that study’s author) and/or to the high concentrations of developmental toxins known to be part of that postnatal exposure (see Section 2. cont.).
A dose-response relationship between an exposure and a health outcome is considered to be especially significant evidence to support a finding of cause and effect. One example of a dose-response relationship involving an early-postnatal exposure, as found in a study by a highly-published scientist, was quoted just above. This finding was even more significant in that it was based on investigation of a very large, diversely-populated geographic area (all 50 U.S. states), and it also applied in relation to numerous smaller-scale units (51 counties). Additional support for a causal connection between this early-postnatal exposure and the outcome of autism was provided by three additional studies, in the U.S., Canada, and the U.K.9
Biological plausibility for a causal connection between this exposure and autism is provided by the recognized vulnerability of the developing brain to toxins during the early-postnatal period, especially in the cerebellum (see Sections 1, intro and 4.a) and by the major transmission of known neuro-developmental toxins via this distinctly early-postnatal avenue of exposure, in doses recognized to be hazardous (see Section 2, cont.).
b) In the first step of another dose-response relationship, a typical fourth child’s risk of autism is half as high as that of a firstborn, and the odds of being diagnosed with autism decrease from first to later children.10 This is a very large, steep progression according to birth order, with no known explanation. In relation to that, it is worth noting that duration of breastfeeding is greater for earlier-born children than for later-born12, and milk received by later breastfed infants has toxin levels that have been reduced as a result of excretion to earlier-born infants during previous nursing.13
At a quick first glance, the chart below could be a graphical representation of autism rates according to birth order.
Neurological toxins typically consumed in infancy decline with birth order, as shown above. The close resemblance of this decline to the decline in autism by birth order might not be coincidental.
In addition to the declines in concentrations of PCBs and DDT with birth order as shown above, concentrations of dioxins in breast milk have also been found to decline with subsequent births, and in percentages similar to those shown in the chart above, as found in a German study described in a 2001 American review article.13a (Remember that, according to a study by an EPA senior scientist, breastfed infants are typically exposed to dioxins, a known neurodevelopmental toxin, in doses scores to hundreds of times higher than established safe levels.29))
c) Decline of eye contact, in a pattern that implicates a specific early-postnatal origin: Eye contact decline, found in infants who were later diagnosed with ASD, was found to begin two months after birth, while normally-developing infants continued to improve. This was seen to be a “derailment” of initially satisfactory development,14 in an area recognized to be very relevant to characteristics of ASD; and it was determined with use of advanced equipment. When looking for a cause of this sudden decline, it seems logical to look at any toxic exposures taking place before the two-month-postnatal turning point. (A 2014 review found that 92% of the studies researching the relationship between environmental toxins and ASD reported a significant association between the two, and 14 of them found a dose-effect relationship.15) When trying to narrow it down as to which sources of exposure to environmental toxins might be most relevant here, it makes sense to focus on the finding of a distinct downturn from normal eye contact to subnormal development (a “derailment”), as opposed to generally below-par progress. This seems to point to a likelihood that toxic exposures related to the downturns would be occurring in the form of relatively sharp increases.
Most fetal/infant toxic exposures are not in the form of sharp increases. They tend to be more stable, such as from living near sources of traffic emissions or other ongoing air pollution, or household smoking, or long-term buildup in a mother’s body. By contrast, there is often a relatively sudden increase in a newborn’s exposures to one source of toxins: Remember that 10 to 20 times as much of a mother's body burden of developmental toxins such as dioxins and PBDEs is transferred to the infant via the milk as by the transplacental route.3 Also remember the major increase in mercury exposure that takes place via breastfeeding.(see Section 2 intro). The timing of the start of these sudden, large increases in exposure to known neurodevelopmental toxins, two months before onsets of derailments of eye contact, suggests a normal period of latency after abrupt exposure increases before distinct turns from good to poor outcomes.
It is of interest that, as autism prevalence in the U.S. has apparently been increasing, and as many child disabilities have without dispute been substantially increasing,3d there have been several-fold increases in the feeding to infants of a certain widely-recommended food.17 That food has been authoritatively found to contain a total of four neurodevelopmental toxins, each in concentrations ranging from well above to hundreds of times established safe levels. (see Section 2, cont. below) The author of this article has written to seven scientists who are employed in the area of neurodevelopmental disorders (the complete science team at Autism Speaks, a major organization involved in autism research), asking whether any of them knew of any source (other than breastfeeding) of toxins to which infants are widely exposed in doses above established safe levels. Of the three replies received as of several months later, none suggested even one other such source of toxins; nor did any of them question the accuracy of the statements about the four developmental toxins being present in human milk in doses far exceeding established safe levels.
But those responses were better than the responses from the physicians’ organizations that promote breastfeeding (associations of pediatricians, obstetrician/gynecologists, and family physicians), which have never responded at all to at least three such letters to each organization.
For more correlations of autism with postnatal exposures, see www.autism-correlations.info.
COMMENTS or questions: At the next link are comments and questions from readers, including seven doctors. Some of the doctors have been critical but others have been substantially in agreement with us (including one with children with asthma, one who says she has delivered thousands of babies, and one with a son with autism); they put into briefer, everyday language and personal terms some important points that tend to be immersed in detail when presented in our own publications. Also, we have responded to many readers’ questions and comments, including about having breast milk tested for toxins and about means of trying to achieve milk that is relatively free of toxins, including the “pump and dump” option. To read the above, go to www.pollutionaction.org/comments.htm
Section 1.a Windows of vulnerability
Describing the brain’s development, the highly-published expert in this field, Philippe Grandjean, refers to “windows of susceptibility to hazardous agents…. Any damage to this ‘wiring’ process can lead to brain damage…. Many of these processes continue until well after birth and some degree of vulnerability (to hazardous agents) therefore continues….” (emphasis and parenthetical expression added) 19 A frequently-cited expert (P. Rodier) describes the extensive postnatal formation of synaptic connections between neurons as well as the postnatal migration of brain cells; also, during this period, the migration process is subject to effects of “toxic agents that lead to migration failure,” which include methylmercury.20 The U.S. Agency for Toxic Substances and Disease Registry (ATSDR) states, “In critical periods of development before they are born, and in the early months after birth, children and fetuses are particularly sensitive to the harmful effects of metallic mercury and methylmercury on the nervous system.”(20a) The NIH’s website echoes the recognition of the early-postnatal period (along with prenatal period) as being a time of “greatest risk” for vulnerability to developmental toxins, since “organ and neural systems are forming” during both periods.21 A commission of the U.S. National Research Council (of the National Academies) refers to “specific periods in development when toxicity can permanently alter the function of a system;” such periods of special vulnerability apply to development of the brain, which the commission says “may demonstrate particular sensitivity during the postnatal period.”(21c) An EPA report to Congress also clearly recognizes the postnatal vulnerability of the developing brain to toxicity of methylmercury,21a and another EPA research report notes that “hypothyroidism during fetal and early neonatal life may have profound adverse effects on the developing brain.”(21b) The latter statement should be read while aware that dioxins, present in breast milk in concentrations scores to hundreds of times the EPA’s established safe level,(29) and mercury (also in breast milk at high levels)(16) are both known to reduce thyroid levels.(44)
The U.S. Agency for Toxic Substances and Disease Registry (ATSDR) refers to “deranged neuronal cell migration” that may result from the developing nervous system’s exposure to methylmercury, during particularly sensitive periods of children’s neurological development occurring in the early months after birth as well as prenatally.(21d)
According to an EPA report to Congress, “Neuronal migration, a process specifically affected by methylmercury, begins at about six weeks in utero, and the process continues until five months after birth (Chi et al., 1977)…. Considering the broad-based impairment of nervous system metabolism that can be produced by methylmercury…, that nervous system development continues postnatally through at least the third to fourth year of life.”(21e)
Another study by Grandjean et al. found “attenuated postnatal growth associated with prolonged breastfeeding,” with greater reduction in growth associated with additional months of breastfeeding, during the first six months after birth. That study found methylmercury to be the specific chemical in breast milk that was most closely associated with the reduced growth, and the growth reduction was measured in relation to the whole body;22 but the reduction was probably especially prevalent in the brain, since (a) methylmercury is known specifically as a neurodevelopmental toxin, (b) it is a metal acting during the period when “the brain is especially vulnerable” to metals,6 and (c) mercury is known to accumulate in the brain; it was found in an experiment with monkeys to accumulate to over seven-times-higher concentrations in the brain than in the blood.23. And it is also likely that the effects would be especially felt in the cerebellum, which would be going through its vulnerable, high-growth period during the first year after birth. (see Fig. 1).
The above Grandjean study was carried out in an island community where ingestion of mercury and PCBs was unusually high (via high seafood consumption), so the effects on overall growth as shown are exaggerated in relation to effects on breastfed infants in the general population; but they may well understate developmental harm to the brain, for reasons given above.
So there is good reason to see these toxins, ingested postnatally, to be causes of (1) toxic effects on the brain during a period of special vulnerability, (2) reduced size of the cerebellum (at least), and (3) very likely also dysfunction in the cerebellum. Remember that both of the latter two outcomes have been extensively linked with autism.
Section 1.b Dioxin (high in breast milk) reduces testosterone, which is important to neurological development: Testosterone is recognized to be important to development of the brain.24,25 According to researchers with both the CDC and the EPA, production of this hormone in infants is quite vulnerable to exposure to dioxin.25 As mentioned above, dioxin is known to be present in breast milk in concentrations scores to hundreds of times higher than the relatively safe dose established by the EPA.29 (It is also present in breast milk at over 100 times the concentration in infant formula.26)
It is known that there is a postnatal surge of testosterone in male infants, but it is not known why that occurs. 27 It is probably not coincidental that this postnatal testosterone surge occurs at the same time as the peak period of growth of the brain (see chart on page 1), the time of occurrence of major neurological development that is known to be dependent on testosterone.24,25 But this is also the peak period of many infants’ exposures to the effects of the testosterone-lowering dioxin, via breastfeeding, in doses far exceeding established safe levels.29 This may help explain why male infants are disproportionately affected by autism and ADHD, since testosterone is clearly more important in males than in females.
Section 1.c Normal formation of connections: A critical part of postnatal brain development, closely linked with ASD, and vulnerable to postnatal toxic exposures:
Neurons are building blocks of the brain, but they only serve their purposes by way of connections to other neurons, and synapses are basic components of those connections. There is substantial evidence of links between neurological disorders (specifically autism) and defective formation of connections in the brain.(27b), (27c) As just part of that evidence, a recent meta-analysis of 25 studies reported data “supporting the theory of specific underconnectivity in autism.” (27a) New studies continue to provide additional verification of such a link.(27d)
The period when those connections are formed is mainly postnatal. That is indicated in a publication of the Life Sciences Learning Center of the University of Rochester, which explains that, “When a baby is born, she has about 100 billion brain cells with short axons and few connections to other neurons. From birth to age 2, new synapses form at the rate of up to 2 million new synapses each second.” (28) There appears to be general agreement that formation of synapses postnatally is very extensive and continues for years after birth.(28c)
A 2013 study, drawing heavily on earlier studies and focusing on the role of environmental chemicals in impairing connectivity, stated that “Data from these studies suggest that the late stages of neurodevelopment, e.g., dendritic growth, synaptogenesis and myelination, are probably most vulnerable.”(27c) (emphasis added) The authors also pointed out that organophosphates (used in pesticides) and PCBs were specifically indicated as apparently adversely affecting formation of connections in the brain. (Remember that this vulnerable stage in the brain’s development is mainly postnatal.)
So there is clearly good reason to focus on the postnatal period as a highly vulnerable period for the process of forming connections, which in turn are closely linked with neurological disorders. Therefore it is especially important to note the extremely high postnatal exposures to toxins that affect the connection-forming process. Two leading experts on toxins involved in child development (P. Grandjean and P.J. Landrigan) have said, “Persistent lipophilic substances, including specific pesticides and… PCBs, accumulate in maternal adipose tissue and are passed on to the infant via breast milk, resulting in infant exposure that exceeds the mother’s own exposure by 100-fold on the basis of bodyweight.”(28f) Prenatal exposure is much closer to “the mother’s own exposure,” as compared with the postnatal exposure that becomes scores of times higher in breastfed infants, as toxins stored in the mother’s fat are mobilized and excreted in the milk.(28g -- also see next section.) And that extraordinary postnatal exposure to connection-affecting toxins starts (at a quickly high level) during the early part of the connection-formation period, in breastfed infants.
To summarize the above-described sequence:
a) Substantial recent scientific evidence points to a link between impaired connections in the brain and neurological disorders, including ASD;
b) there is general agreement that formation of connections in the brain is largely or predominantly a postnatal process;
c) many studies indicate that postnatal neurodevelopment is the most vulnerable period for formation of connections; PCBs and pesticides are especially implicated as having toxic effects on this process;
d) those and other neurodevelopmental toxins accumulate in a woman’s body over many years, and are excreted in breast milk in greatly concentrated form, early in the postnatal period when connections are being formed in the infant’s brain.
Section 2 , cont.: Exposures to neuro-developmental toxins are often extraordinarily high in the early-postnatal period, by comparison with established national or international standards and also in relation to prenatal exposures:
-- dioxins, in human milk in concentrations exceeding the EPA’s Reference Dose (estimated reasonably safe dose, or RfD) by scores to hundreds of times;29
-- PBDEs, in breast milk in concentrations normally well above and sometimes up to 40 times the EPA’s RfD;30 and
-- PCBs, in human milk in concentrations about 20 times the maximum allowed by law in U.S. public water supplies.31a
-- Mercury concentrations in human milk typically eight times the WHO guideline for drinking-water quality;(30a) remember from Section 2 intro about the dramatic increases in mercury transfer to infants that take typically take place right after birth.
All four of the above developmental toxins(31b) are present in infant formula in average concentrations no more than 4% as high, and usually less than 1% as high, as their concentrations in human milk.32 Inquiries to a number of scientists involved in neurodevelopmental disorders have indicated that apparently nobody knows of any other avenue, other than breastfeeding, to which the developing brain is widely exposed to any toxins in doses exceeding established safe levels.32a
Notice on the right the difference (shown in the gray area) between the PCB exposures of breastfed children (peaked lines) and those of cow’s-milk-formula-fed children (drooping lines). (This chart is from a 2011 study, Quinn et al.,33 by a Canadian-Swedish-Norwegian team of scientists; similar data are shown in a 2015 study.33a) Seeing the peak at 6 months, corresponding to the 6-month duration of breastfeeding assumed for this chart, consider how high the extra PCB exposure would be if the infant were to be breastfed for (the often-recommended) 12 months or longer. Also bear in mind that PCBs are only one of four developmental toxins to which breastfed infants are exposed in doses far exceeding established safe levels, and at far higher levels than formula-fed infants. (see above)
Not surprisingly, there are effects of developmental toxins ingested postnatally:
PCBs: A large team of German scientists and doctors, studying 171 healthy mother-infant pairs, found "negative associations between (human) milk PCB and mental/motor development ... at all ages, becoming significant from 30 months onwards." Also, "negative associations with PCB increased with age." They found no significant association of the children’s neurological development with PCB levels in umbilical cord blood, whereas they did find association with breast milk PCB concentrations and duration.66 For results of many other studies showing associations of postnatal PCB exposure with adverse neurological effects, including three additional studies that at the same time found no effects of prenatal exposures to PCBs, see PCBs in Appendix A.
Dioxins: A study by an international research team (Lee et al.) found that learning disability and attention deficit disorder were 133% and 202% higher among children with higher levels of dioxins -- that is, over two and three times the risk compared with children with lower exposures.47a The elevated levels of dioxins associated with such dramatic increase in risk of neurological disorders were quite common -- found in 27% to 31% of children -- by no means exceptional exposures. And these elevated levels of dioxins were almost certainly of early-postnatal origin, given the following:
In a 2011 study, by 13 scientists, it was determined that the median levels of dioxins in breastfed infants were doubled within 4-5 months after birth, compared with levels in formula-fed infants that were reduced by half in that same period of time; after those infants had grown to ages18 to 26, average dioxin concentrations were still twice as high in the breastfed young men as in those who had been formula fed.(66a) In another authoritative study, the breastfed-to-formula-fed ratio of dioxin accumulation was calculated to be 6-to-1 after the first year for infants breastfed 6 months or more, and still 2-to-1 a decade later.(26)
For several other studies indicating associations of postnatal dioxin exposure with adverse effects, including two studies that found no effects of prenatal exposures to the same toxins, see the “Dioxins” section of Appendix A.
PBDEs: A Spanish study assessed PBDE levels in mothers and found that gestational exposure had no significant adverse effect on 4-year-olds, but exposure to those same mothers' PBDE levels via breastfeeding did have a substantial effect, including an 80% increase in relative risk of attention-deficit problems and a 160% increased relative risk of poor social competence.72 (“Poor social competence” is a way of describing typical characteristics of people with the autism spectrum of disorders, or ASD.) Note that this study was carried out in Europe, where PBDE levels have been found to be one-tenth (or less) as high as in the United States.72a For additional studies finding associations between postnatal PBDE exposure and adverse neurological effects, see the PBDEs section of Appendix A.
Mercury: At least six published studies have found high levels of mercury in those diagnosed with autism.85 For information about (a) close similarities between very specific known effects of mercury exposure and traits of ASD, (b) the recognized postnatal vulnerability of brain development to the effects of mercury, and (c) the known latency of effect of mercury that is very compatible with the surprising regressions and late emergence of ASD traits following earlier normal progress, see www.autism-correlations.info. That includes information about a major study and its sequel, both of which found no effects of prenatal exposure to this well-known neuro-developmental toxin.
Some studies, while not disputing the high levels of toxins in human milk, have found no harmful effects to result from those toxins; but those studies have suffered from various problems -- testing at too young an age, not testing for important impairments, confounders, etc. -- see Section 5, cont.
Immunity-related diseases (diabetes, asthma and allergies) and ADHD,36 mental difficulties among boys,37 and apparently mental retardation38 and autism have been increasing among children, and no causes of those increases have been confirmed. Since there have been undisputed increases in a type of infant feeding (breastfeeding)17 that is known to contain hazardous concentrations of developmental toxins (see above), with some or most of those toxins increasing in the environment and therefore in women’s bodies,40 there ought to be recognition of the possibility that those increasing toxic exposures could be having harmful effects on some infants. That is especially the case since other confirmed causes of the above-mentioned epidemics and increases of disorders have not been found.
For over 30 studies that found harmful effects of postnatal exposures while finding less or no effects of prenatal exposures to the same toxins, see the studies marked with asterisks, mainly in Appendix A but also some of the studies listed just below here.
*-- A 2013 study found significant effect of prenatal exposure (to traffic-related pollution, associated with autism), but over twice as much harmful effect associated with postnatal exposure: Volk et al., Traffic Related Air Pollution, Particulate Matter, and Autism, JAMA Psychiatry. Jan 2013; 70(1): 71–77, at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019010/
*-- A 2010 study (Verner et al.) assessed infant blood PCB-153 levels at delivery and on a month-by-month basis during the first year of life in a longitudinal birth cohort. “Whereas inattention was related to prenatal exposure, activity level (non-elicited activity -- considered to be impairment) was best predicted by postnatal exposure….. These findings are consistent with previous reports indicating PCB-induced behavioural alteration in attention and activity level.”(40a) (italics and parenthetical expression added)
-- A Taiwanese study summarized information regarding effects of PBDEs as follows: “Neonatal BDE-209 exposure has been demonstrated to have neurotoxic effects in most in vivo studies. Neonatal exposure to BDE-209 has been found to have developmental neurotoxicity, including hyperactivity; learning and memory defects; a reduction in habituation;… The results of this study show that infants exposed to BDE-209 probably experience developmental delays in cognition.”42
-- A research group (Schantz et al.) found an association between the amount of PCBs in breast milk and developmental scores: as PCB concentrations in the mother’s milk increased from the 5th percentile to the 95th percentile, scores on the Bayley MDI decreased by 9.9 points.67 These tests are scored on a scale like that used for IQ tests, such that a 9.9-point decrease would be the distance between the center of the range in the population and the upper end of the bottom quarter, a very substantial decline. And that major decline apparently resulted merely from higher concentrations of PCBs such as are found in breast milk ingested by many thousands of infants, even without taking into account effects of different durations of breastfeeding.
-- A study of children of 8000 mothers who ate Lake Michigan fish (Jacobson et al.) found that “Higher PCB concentrations in breast milk were … associated with poorer performance” on tests measuring both verbal and numerical memory.66c Again, this found effects of merely higher concentrations of the toxins in breast milk, without taking into consideration effects of longer durations of breastfeeding.
*-- In a study carried out in the Seychelles (Davidson et al., 2010(70n) ), investigating children exposed to mercury by way of high seafood consumption, it was found that prenatal exposures had no significant effects, but postnatal exposures did appear to have substantial adverse effects on male children when tested at ages 9 and 17. (See charts.)
On the left are large sections of Figures 1 and 2 from the above-mentioned study, consolidated here. Results are shown for a number of different scholastic achievement tests administered to children who had varying levels of mercury; for six of those tests, results were indicated by gender (as seen in these charts). The tests that were not broken down by gender showed no consistent associations of mercury with achievement, in contrast with the results that were shown separately for males and females, in these charts. The authors acknowledged what is undeniable in these charts by saying, “we did find significant adverse associations between recent postnatal MeHg (methyl mercury) hair level and outcomes” in boys only, which they said was compatible with a report of “some adverse effects” of postnatal MeHg exposure. But beyond that they said little more than that the gender effects were “intriguing,” that their “findings are sporadic and not consistent,”(!) and that “this outcome does not constitute evidence of any pattern of associations between MeHg and achievement.” While reading those surprising words about “sporadic and not consistent” findings and about lack of any pattern, note that these charts are the only reports in this study that provided results for males and females separately.
The above would seem to be a good illustration of researchers’ only seeing or reporting things that fit their preconceived ideas. It is apparent that there is a widespread, firmly-held but unjustifiable notion among many scientists that only prenatal, rather than postnatal, toxic exposures contribute significantly to adverse neurological effects in children. When other scientists or medical professionals read only the abstracts or news reports about studies such as this, the preconceived notions are inappropriately reinforced. To read more about the authoritatively-recognized problems of researchers’ biases and distorted reporting of findings, see Appendix B.
At a time when diagnoses of both autism and ADHD have been increasing rapidly, with both affecting males overwhelmingly, it would seem that results such as those in all of these charts should not be merely dismissed as “sporadic,” and (by implication) not significant. But it appears that many scientists (and peer reviewers) will not be able to see the obvious until progress is made in overcoming the groupthink belief that only prenatal exposures have serious developmental effects.
To read about a major 2013 study that, like this one, found serious adverse effects of developmental toxins on boys while finding favorable effects on girls, as well as many other studies that found harmful effects on males while not finding harmful effects of the same toxins on females, to read a biological rationale for these effects, and to consider what could well be widespread consequences of this phenomenon in obscuring evidence of harmful effects of toxins to which developing brains are exposed postnatally, see Appendix C.
To permit moving on now to the other main points of this article, a presentation of many other studies that found links between postnatal toxic exposures and later developmental harm are continued in Appendix A.
5.a Inaccurate assumptions about the duration of the brain’s period of major development, resulting in researchers’ paying no attention to early-postnatal exposures as causes of adverse effects: Authors of major studies on effects of maternal mercury in the Seychelles Islands (Myers and Davidson) explained why their studies and others looked essentially only at prenatal exposures, saying, “The focus of these studies was on prenatal exposure and its association with child development because the developing brain appears to be most sensitive to the effects of MeHg.” 66d So, even to these well-published scientists, a developing brain is essentially a prenatal brain. That supposition may have been in accord with the existing knowledge in earlier decades but it conflicts fundamentally with more recent research. (see Figure 1 and the text below it and Section 1, cont.) And that improper assumption caused these scientists to not look for -- and therefore to not see -- effects of postnatal exposure; Figure 5 and accompanying text provides what appears to be an example of Davidson’s failure to see what ought to be obvious, regarding effects of postnatal exposures. In a similar vein, the director of the CHARGE study in California has been quoted as pointing to the likely vulnerability of the process of synapse formation and considering this to be essentially a prenatal occurrence;(28e) but current knowledge indicates that postnatal synapse formation is very substantial and continues for years after birth, probably far exceeding prenatal formation. (see Section 1, cont., 1.c). So inaccurate assumptions about the duration of the brain’s developmental period cause researchers to unduly narrow their fields of investigation and to fail to observe associations of postnatal toxic exposures with adverse effects.
There appears to be a general inclination to avoid considering the subject of early postnatal vulnerability to developmental toxins. Most research requires funding from sources that conspicuously promote breastfeeding, including the U.S. government, To read about authoritative recognition that “claimed research findings may often be simply accurate measures of the prevailing bias,” see Section 1.c of www.breastfeeding-studies.info)
5.b Recognized confounders that are not acknowledged or controlled for: Referring to the “striking deficits in several cognitive tasks” on the part of animals postnatally treated with PCBs in doses similar to those in human breast milk, as well as to findings of other studies, authors writing in Environmental Health Perspectives pointed out probable reasons why similar effects were not found in some studies of human children: the mothers of the breastfed children were known to have been more highly educated, with higher IQs, and provided more stimulating home environments, all of which would have been expected to provide upward bias in tests of the breastfed children, canceling out the negative effects of PCBs in their milk.45 Providing support for this explanation about the role of confounders, other authors state, ”both studies that did not find effects (of developmental exposure to PCBs) on IQ (CPP and North Carolina) did not control for quality of parenting as measured by quality of home environment and parental verbal abilities. These variables were included in the analyses from the Michigan (11-year assessment), Oswego, Netherlands, and Germany cohort studies, all of which found significant effects” of developmental exposures to PCBs.57c Note that the authors found only two studies that failed to find adverse effects of PCBs on IQ, and neither of those studies had controlled for the well-known confounder, quality of parenting. Confounders are the principal reason why studies can reach “false conclusions,” in the words of the U.S. Agency for Healthcare Research and Quality.46
5.c Many studies that have found effects of what they call “prenatal” exposures were actually finding effects that could also have been effects of postnatal exposure; but that is not acknowledged. It is common to test for toxins in umbilical cord blood or in mothers’ bodies in the third trimester and even to examine breast milk contents and to use those measurements solely to indicate “prenatal” exposures.58a Those same measurements would have been as good or even better at indicating postnatal exposure via breastfeeding; that is especially true considering that (a) most women have been breastfeeding their infants in recent decades, and (b) transfers of a mother’s accumulations of toxins to infants via lactation increase many times over compared with transplacental transfers.(see Section 2.a), and (c) as amply indicated earlier (see Section 1), the brain is still actively developing postnatally (especially forming connections) and is therefore quite vulnerable to effects of toxins far into the postnatal period. But the adverse effects of those toxins, ingested much more intensely postnatally than prenatally, are regularly attributed in studies only to “prenatal” exposures, with no acknowledgement that they could also originate or greatly increase postnatally as a result of exposures via breastfeeding.
5.d There is evidence that at least some toxic effects thought to be “prenatal” in origin are actually only results of postnatal exposures: There have apparently been only two studies that have found no neurological harm to children to be associated with elevated maternal levels of mercury at time of birth; both of them were carried out in the Seychelles, where postnatal exposures to maternal mercury (via lactation) were exceptionally low.58b The Seychelles findings have received considerable attention, since they were at odds with the findings of neurological toxicity of maternal mercury in at least eight other studies; expert testimony to the U.S. Congress stated that the findings in the Seychelles were “anomalous” in relation to the findings in many studies carried out in other parts of the world.57e It is noteworthy that breastfeeding rates in the Seychelles were apparently exceptionally low at the time when the subjects in the studies in that country were born;57f therefore exposures to maternal mercury levels in the Seychelles (relevant to these studies) would have been substantial prenatally but not postnatally. One could reasonably infer that the recognized developmental toxicity of moderately-elevated levels of mercury is not significant unless there is substantial exposure to it postnatally. (Such exposure normally takes place via breastfeeding in most countries (see Section 2, cont.)). This would be biologically plausible not only because ingestion of mercury is known to be especially high postnatally, via breastfeeding, but also because of special postnatal vulnerability of connection formation (see Section 1.c), as well as the recognized increased vulnerability to metals of the developing brain during the brain growth spurt.57g (See the brain’s growth spurt, especially of the cerebellum -- linked with ASD -- mainly taking place postnatally, in Figure 1.)
5.e Studies completed too early to allow observation of long-term effects of neurologically-toxic exposures that are known to often have long latent periods (extending to decades) before effects become noticeable.57, 57a As was reported in a 2009 study, “PCBs were not related to global IQ at 4 years of age in the Michigan cohort but were at age 11 years (Jacobson et al. 1990; Jacobson and Jacobson 1996). Similar results were obtained in the Oswego study (Stewart et al. 2003b, 2008).” 57c Along such lines, the U.S. ATSDR says there is good evidence that methylmercury has “delayed neurotoxicity observable many years after cessation of exposure.”57b
A council of experts consisting of ten Phd's and three MD's, all of whom are university professors, attacks the myth that assumes “that the absence of cognitive or behavioral problems in childhood indicates that an early exposure to a neurotoxin had no adverse effect on brain development.” They refer to studies demonstrating that some substances cause damage to the brain that result in delayed onset of neurological problems, with ”long-term consequences.”(47d) Another large team of experts and researchers indicates strong support for the hypothesis that infant exposures to toxins could result in reductions of neurons or damage to brain cells that could have no visible consequences while there is still a surplus of functioning cells, and only several decades later, when normal reductions of brain cells occur, would the early damage lead to Alzheimer’s or Parkinson’s diseases.(47e)
Note that many studies test children at early ages and declare that no harm has resulted from toxic exposures via breastfeeding, assuming that this is all that needs to be known about the effects of those early exposures.
Studies that assessed apparent effects of developmental toxin exposures on children in their teenage years are extremely unusual; assessments at that age should be expected to provide far more meaningful evidence about long-term effects of developmental toxins, compared with the typical studies that involve only young children. One such study was the Lee study (mentioned in Section 2.cont.); that study found dramatically increased rates of learning disability and attention deficit disorder among 12-to-15-year-olds with higher levels of dioxins.47a And those higher levels of dioxins with such major apparent effects were relatively typical levels, found in about 30% of the population. This indication of long-term effects should be seen together with the authoritative evidence (from a study by a two-person team headed by a senior EPA scientist) indicating that higher levels of dioxins are closely linked with early-postnatal exposure even in later childhood: accumulated exposures to dioxins, at ten years of age, were determined to still be twice as high among children who had received six or more months of breastfeeding as among non-breastfed children.47b
5.e Studies begun too late to detect important toxic exposures that occurred during the critical early postnatal period of vulnerability to neurodevelopmental toxins; the neurodevelopmental toxin mercury, for example, is ingested by breastfed infants in especially high concentrations during the very vulnerable early postnatal period,30a, 31 but it has a half-life in the body of only 60-90 days.58 Typical studies measure mercury levels in children several years old or older, when the relatively brief period of greatest exposure and vulnerability is far in the past, and then state or imply (on the basis of their current observations) that mercury has no effects postnatally. Examples illustrating this point are found in Appendix B
5.f Testing only for a very narrow range of impairments, finding none, then declaring or implying that the undisputed high concentrations of developmental toxins in breast milk do not have adverse consequences: It is typical for researchers to do two or three specialized tests, without testing for
(a) social competence (central in Autism Spectrum Disorders, or ASD),
(b) language ability and other communication skills (also central in ASD),
(c) attention deficits or hyperactivity (which are at the core the of the major, increasing disorder, ADHD, traits of which also overlap with traits of ASD49),
(d) immune dysfunction: dozens of studies have found positive associations between breastfeeding and immunity-related disorders,51 and associations have been found between autism and immune system irregularities.52
(e) Long-term memory (basically, learning ability); mercury administered in low-moderate doses to infant rats was found to seriously impair long-term memory, even though the juvenile rats were unimpaired in following cues. “Animal and human studies have identified motor and sensory deficits with increasing age that were not seen at earlier time points after the cessation of exposure (to mercury and PCBs), as well as a worsening of conditions with age.” Poor impulse control, which could lead to poor academic performance, accidents, and criminal activity, is suspected to be related to environmental toxins, and is also not part of normal testing.52a
(f) Obesity and diabetes, both of which have been found in many studies to be associated with high levels of PCBs,52b which in turn are unusually high in breastfed children. PCB levels in children who had been breastfed for at least 12 weeks were found to be still over twice as high as in bottle-fed children even at 7 years of age. (This is stated together with other relevant evidence and authoritative sources in Section 1.a of www.breastfeeding-toxins.info,) Also see the chart at the beginning of Section 2, cont., above. Also see the Schell study in the PCBs section later about increased PCBs in breastfed children.
(g) Reproductive effects, which experiments with animals have found to be associated with high PCB levels. (See (f) above about high PCB levels in breastfed children.) Effects that have been found have included, among others, lower reproductive organ weights in exposed males, lower numbers of sperm in exposed males, lower number of exposed females mated, fewer completed pregnancies, lower reproductive organ weights in offspring, and impaired function in offspring.52c At a time when birth rates are well below replacement levels in most developed countries (the U.S. is an exception, because of the large number of foreign-born mothers), this should be of concern.
(h) Gradual degradation of organs that could well lead to observable harm in the long run but not in the near term; one logical explanation for the observed greater long-term effects of PCBs 57c (which are very high in breast milk) has been provided by the finding that PCBs disrupt the blood brain barrier, as stated in studies published in 2010 and 2012.53 This leaves the brain more vulnerable to effects of background environmental toxins that could gradually accumulate in the brain over the course of many years, especially as the child’s exposure to the environment increases.
For continuation on this topic, including about ”selective or distorted reporting” in studies (according to a highly-placed doctor and scientist), publication bias, and the influence of “prevailing beliefs” among scientists that prevent recognition of effects of low doses of toxins (according to another eminent doctor/scientist), go to Appendix B. That appendix also contains examples of studies that have improperly promoted misconceptions about prenatal vs. postnatal exposures.
. . . . . . . . . . . . . . . .
Based on statements from many experts on neurological development, the early-postnatal period is a period of critical vulnerability of the developing brain to toxic exposures. Most infants these days are routinely fed a substance (human milk) that, in developed countries, usually contains developmental toxins in authoritatively-recognized hazardous concentrations. Many scientific studies (with humans as well as animals) have found substantial adverse outcomes (often in a dose-response relationship) following infant exposures to these toxins, after early-postnatal exposures to concentrations similar to typical human infant exposures.
There are unexplained increases in various childhood neurological disorders for which causes are being sought; and there are widespread early-postnatal exposures of infants to developmental toxins in recognized hazardous concentrations but without recognized effects. But few people seem to be seeing a connection between the disorders with no known causes and the early-postnatal toxic exposures with no recognized effects. There is substantial evidence, presented above, indicating that the early-postnatal toxic exposures are having harmful effects, and that those effects are being overlooked.
Authorities to whom people have a right to look in expectation of receiving truthful information (doctors’ associations and government health authorities) are telling only half-truths on this subject, withholding information about the undisputed high levels of toxins in human milk and the reasons to believe that those toxins are having harmful effects. When such things are pointed out to those agencies (in repeated letters from the director of Pollution Action), government officials merely refer to the positions of the doctors’ associations and WHO, and the latter organizations never respond at all. The responsible authorities do not deny the negatives of breastfeeding, they merely do their best to conceal them from parents.
Early-postnatal exposures to developmental toxins have another especially important characteristic:
They are widespread, hazardous infant exposures that could be greatly and quickly reduced, if parents were merely to become adequately informed about toxins present in a very common type of infant feeding.
-- High infant exposures to serious developmental toxins (listed in Section 2, cont.) could be avoided by parents’ reverting to a type of infant feeding that was the predominant feeding type in the mid-20th century,62 without negative health effects’ being apparent as of a half-century later. (See below for comparisons with later periods.)
-- Four decades of historical child health data (mainly from the CDC) have shown that the major increases in breastfeeding rates since 1971 have been followed by substantial increases in all but one of the disorders that are alleged by the U.S. Surgeon General to be reduced by breastfeeding.63
-- Epidemics and increases of other childhood disorders (diabetes, asthma, allergies, obesity, ADHD and apparently mental retardation and autism) came about following the transition from low to high breastfeeding rates.64
-- Good reason to see a reversion to mainly bottle-feeding as a reasonable alternative, compared with the type of infant feeding that is high in known neuro-developmental toxins, can be found in
-- the historical record (see above),
-- the 50+ studies that have found adverse effects of breastfeeding,65 and
-- the increasingly wide acceptance of the “hygiene hypothesis” as an explanation for the increases in immunity-related diseases among children;65a according to this hypothesis, microbial exposure in contemporary developed countries (due to increases in hygiene in recent times) is already too low to provide the needed stimulus for proper development of children’s immune systems; the additional shielding of infants from microbes as provided by the immune cells in breast milk should be seen in that light.
Note well the many studies (in addition to the Davidson study at Section 3, cont) that found associations of adverse effects with postnatal exposures while finding less or no associations with prenatal exposures to the same toxins; those studies are marked below with *.
Dose-response relationships between postnatal exposures and effects related to child development:
Especially strong evidence of causation is found in dose-response relationships, such as those below that found associations of adverse effects with postnatal exposures to be greater when linked with greater postnatal exposures, as follows:
-- The 2003 Grandjean study, which was the source of the “Attenuated growth” chart earlier, was one example of a dose-response relationship found with regard to a distinctly postnatal toxic exposure.
-- The Shamberger study mentioned in Section 6 found a dose-response relationship between autism and exposure to breastfeeding.
*-- A 2014 study found that levels of developmentally-harmful PCBs in children increased greatly with increasing duration of breastfeeding, and “postnatal rather than maternal or cord PCB concentrations were associated with poorer performance on otoacoustic (hearing) tests at age 45 months.”43b
-- As mentioned at the end of the “Immunological problems” section below, seven studies have found dose-response relationships between allergies and breastfeeding.
-- As mentioned in the “Other studies” section below, a review study reported that seven studies found a dose-effect relationship between heavy metal concentrations from various tissues/body fluids in children and ASD.80a
-- A 2009 study of effects of mercury exposure found that “In the primary analysis at 107 months there were four postnatal associations present. All were in the direction of declining performance as (postnatal) exposure increased.”(6b)
-- A dose-response relationship between postnatal PCB and lead levels and correct responses or slowing of responses was found in Boucher et al., as seen in Figure 1 of that study.71c
-- A 2001 study of 180 adults (Schantz et al.,, 2001) many of whom had received PCB exposure via eating Great Lakes fish, found that, “after controlling for potential confounders PCB, but not DDE, exposure was associated with lower scores on several measures of memory and learning.”41d “A clear downward trend in verbal recall scores was seen with increasing PCB exposure,” and that was also the case in the scores from two other tests.
-- See the Ettinger and Lozoff studies in the lead section later in this appendix.
-- See the Gascon et al. 2011 study in the PBDEs section later in this appendix.
-- A Dutch study found that longer breastfeeding duration was associated with lower scores in 9-year-olds on a test of problem solving.66b
-- Referring to an earlier study, a 2014 study in the journal Pediatrics reports that teacher ratings revealed a “significant association between increasing breastfeeding duration and conduct disorder ratings at 7 years.”(66e)
-- The 2006 Lackman et al. study found that increases of PCBs and other hazardous organochlorine compounds in infants were very substantial with six weeks of breastfeeding but were far greater still with six months of breastfeeding. (71e)
-- The Schantz et al. and Jacobson et al. studies in Section 3.cont. would probably also be properly considered to be among studies that found greater effects associated with greater postnatal exposures to toxins.
(When reading the next several summaries, note that ADHD, as well as attention deficits and hyperactivity as separate categories, have been found to overlap with autism, in addition to themselves being widespread, increasing, and serious neurological disorders. According to a German research team, “Inattention, impulsivity and hyperactivity are amongst the most frequent associated symptoms of ASD.”71)
*-- A Spanish study (Gascon et al. 2011) assessed PBDE levels in mothers and found that gestational exposure had no significant adverse effect on 4-year-olds, but exposure to those same mothers' PBDE levels via breastfeeding did have a substantial effect, including an 80% increase in relative risk of attention-deficit problems and a 160% increased relative risk of poor social competence.72 (Note that “poor social competence” is a way of describing typical characteristics of people with ASD.)
-- A 2012 study found that children who had consumed breast milk that was merely in the two upper quartiles in PBDE levels were 2½ to over 3 times as likely (compared with those below median) to have high scores in activity/impulsivity behavior, of a kind that indicated likelihood of developing into ADHD.74
-- Another observed example of a dose response to early-postnatal exposure can be found in the following: Another study (Gascon et al. 2012) found “an association between PBDE concentrations in colostrum (early breast milk) and impaired infant cognitive development." The authors also pointed out that “in the group of children breastfed for a longer period the association between BDE-209 exposure and neuro-development impairment was somewhat stronger…. Further, associations in the longer breastfeeding group may be underestimated because the higher social class and education level of these mothers may provide a more advantageous environment for neuro-development.”68
-- A 2014 study found that “the majority of the epidemiologic evidence supports that early life exposure to PBDEs measured during pregnancy and/or during childhood is detrimental to child neurodevelopment in domains related to child behavior, cognition, and motor skills.”68e This should be seen in combination with awareness of the high levels of PBDEs in breast milk in relation to established safe levels and in comparison with levels in infant formula. (see Section 2.cont.)
-- A 2007 study of experiments with animals observed that “Levels of PBDEs causing developmental neurotoxicity in animals are not much dissimilar from levels found in highly exposed infants and toddlers.”68f
*-- A Danish case-control study of 95 cryptorchid boys found a relationship between PBDE measured in breast milk, but not placenta, and risk of cryptorchidism.68d (Note that cryptorchidism can be acquired after birth.)
-- A 2013 study provides additional evidence of causal effect of childhood PBDE exposure on ADHD-like behavior.86
--- Remember the Taiwanese study that found postnatal effects of PBDEs, in Section 3, cont.
Other postnatal exposures associated with ADHD effects (in addition to those mentioned in the previous section):
A study of Chinese children with elevated mercury levels due to fish consumption found that the children with mercury concentrations above a certain level (one-sixth of the level considered to be poisoning) had a 9.7 times higher risk of having ADHD, after adjustment for confounding variables. Also, after adjusting for age, gender and parental occupational status, the mean blood mercury level was found to be 75% higher in children with ADHD (p < 0.001)68a
Also see the Lee study in the upcoming Dioxin section.
-- A major text published in 2011, with 21 contributing authors, states as follows, referring to dioxins (on p. 551), “early developmental exposures to these chemicals are particularly devastating.” (on p 559): “These studies have indicated that … the most susceptible period of exposure is during development and nursing.”…. “Several epidemiological studies have indicated that exposure to PCBs can contribute to hyperactivity and may contribute to the prevalence of attention deficit hyperactivity disorder (ADHD) in humans (Bowman et al., 1981, 1981; Rice, 2000; Hardell et al., 2002).” (68b)
A study published in 2015 found early postnatal as well as prenatal exposures to PAHs to be associated with reduction of white matter in the brain, which in turn was associated with symptoms of ADHD. 68c
*-- A large team of German scientists and doctors, studying 171 healthy mother-infant pairs, found "negative associations between (human) milk PCB and mental/motor development ... at all ages, becoming significant from 30 months onwards." Also, "negative associations with PCB increased with age." They found no significant association of the children’s neurological development with PCB levels in umbilical cord blood, whereas they did find association with breast milk PCB concentrations and duration.66 (Walkowiak et al., Environmental exposure to polychlorinated biphenyls and quality of the home environment: effects on psychodevelopment in early childhood. Lancet 2001: 358: 1602-07 Abstract at www.thelancet.com/journals/lancet/article/PIIS0140-6736(01)06654-5/abstract)
*-- A Dutch study (Patandin et al.) found a strong association of exposure to PCBs specifically via breastfeeding with problems of inattention and hyperactivity in children at 42 months of age. The study distinguished between effects of prenatal and lactational exposure, and found that only the lactational exposure was associated with “less sustained attention” as well as slower reaction time.73
-- According to a 2011 study by a German scientist (Winneke, with the Division of Neurobehavioral Toxicology, Medical Institute of Environmental Hygiene, Heinrich-Heine-Universität), “Several prospective cohort studies…have demonstrated that pre- and early postnatal exposure to PCBs is associated with deficit or retardation of mental and/or motor development….”41
-- A 2015 study by a team of six scientists refers to “the extensive brain development that occurs postnatally, including cell differentiation that has been shown to be altered by PCBs ….”41b
-- A 2004 Dutch prospective study (therefore allowing accurate measures of exposures, compared with retrospective studies) investigated mental abilities of nine-year-old children in relation to their histories of breastfeeding versus formula feeding; the authors grouped the children into six different categories, according to shorter or longer durations of breastfeeding, formula feeding, and higher or lower exposures of each of those groups to prenatal toxins. The formula-fed children performed better than their breastfed counterparts, and the children who were breastfed for longer periods performed worse than those breastfed for shorter periods, in scores on a test of executive function. Those relationships held consistently, when the subjects were grouped according to both higher prenatal exposures to toxins and lower prenatal exposures to toxins. Scores of formula-fed children were only insignificantly higher than those of children breastfed for shorter durations (6 to 16 weeks).41c
Describing the test (Tower of London test) that was used in the above study, the authors said, “these tasks are complex, multifactorial tasks, and performance may reflect frontal lobe functions as well as more posterior-related functions. For example, performance on the TOL requires functions such as planning, spatial working memory, attention and response inhibition, and the ability to relate and integrate isolated details into a coherent whole, as well as spatial and motor abilities…. (Such studies) showed activation during performance on the TOL in other brain areas….,” enumerating five other brain areas in addition to the frontal lobe that were observed to be active with this kind of test.41c This study apparently provided better evidence of neurological effects of formula-feeding versus breastfeeding than most other studies of effects of breastfeeding, since it tested children at a relatively advanced age (9, therefore providing better evidence of long-term, lifetime-relevant effects) and since the test was relevant to a greater range of mental activities than typical tests.
-- Another study (Schell et al.)43a is relevant to neurological development because development of the brain is known to be heavily dependent on testosterone;24,25 the authors found that a 10% increase in exposure to PCBs was associated with a 5.6% decrease in testosterone. These results were said by the authors to be consistent with findings of four animal studies and six studies of humans. Those percentage differences should be seen in relation to studies (cited by the U.S. ATSDR) finding over 20-times higher concentrations of PCBs in breast milk than in formula.78 Also note that, as found in a study published in 2014, children at 45 months of age who had been breastfed for 6 to 12 months were found to have over 9 times the PCB concentrations compared with non-breastfed children, with even greater differences if the children had been breastfed for longer.43b If a 10% increase in PCB exposure is associated with a decrease in testosterone of almost 6%, consider the effect of a difference of several hundred percent in PCB exposure. So a frequent, distinctly early-postnatal exposure dramatically increases a child’s ingestion of a chemical that apparently greatly reduces the infants’ supply of a developmentally-important hormone.
-- A 2010 review article (Eubig et al.) generalized that “children and laboratory animals exposed to lead or PCBs show deficits in many aspects of attention and executive function that have been shown to be impaired in children diagnosed with ADHD, including tests of working memory, response inhibition, vigilance, and alertness.”(43c) This should be considered together with knowledge of the tremendous increase in PCB concentrations in children due to breastfeeding (see above).
-- As presented in a document of the U.S. ATSDR, monkeys exposed from birth to age 20 weeks to PCB mixtures of congeneric composition and concentration similar to that found in human breast milk showed learning deficits long after exposure had ceased (Rice 1997, 1998, 1999b; Rice and Hayward 1997, 1999a). This type of study appears to be the most relevant to evaluating risk of PCB exposure by infants since they mimic the exposure scenario for a nursing human infant.” (U.S. ATSDR document on PCBs, Section 3.7, p. 381, at http://www.atsdr.cdc.gov/ToxProfiles/tp17.pdf)
-- When looking at other studies that are related to postnatal exposure to PCBs, the reader should remember that impulsivity is one of “the most frequent associated symptoms of ASD.”71 Various studies have found impulsivity, or impaired inhibition or control of behavior, or “excessive or inappropriate responding” to be associated with prenatal exposure to PCBs;71a, 71b those studies generally did not investigate effects of early-postnatal exposures to toxins. Only one study can readily be found that assessed impulsivity-increasing effects of both postnatal and prenatal exposures to PCBs, as follows:
*-- Boucher et al. found effects of postnatal exposures to PCBs (underlined in the chart below) to be significant (as indicated by the notes referred to by asterisks) whereas effects of prenatal exposures (shown under “Cord plasma”) were mixed, small, and did not reach statistical significance (no asterisks).71c
(Note that Pb is the chemical abbreviation for lead, and Hg stands for mercury. PCB-153 exposure was the focus in this study since its levels are considered to represent presence of other PCB congeners fairly accurately.)
Since high lead levels have been found to be associated with delinquency and criminal activity,71d it should not be surprising that higher lead levels were found to be significantly negatively associated with a measure of inhibition of actions, as shown above. What may be surprising to some is that postnatal exposure to PCBs appears to have a stronger effect than exposure to lead in impairing inhibition of behavior, in this study. (PCB levels in this study area are higher than in many locations but are, according to the authors, “similar to those in the Dutch PCB study (Longnecker et al. 2003)”.
Postnatal exposure to PCBs also had apparent effects of slowing the responses of the tested children in the Boucher et al. study, effects that the authors of the above study said “seem linear.”71c In other words, the greater the postnatal exposure, the greater the apparent effect of slowing the responses, another dose-response relationship found in a postnatal toxic exposure. (See Figure 1 in that study.) The effect was not large among the children tested, but bear in mind that the severity of the effect could increase with age, as has been found to be the case with effects of PCBs on IQ, in several studies.57c Any slowing of responses might well make the difference between avoiding a serious vehicle accident and not avoiding it.
*-- Lynch et al., The effect of prenatal and postnatal exposure to polychlorinated biphenyls and child neurodevelopment at age twenty four months, Reprod Toxicol. 2012 Nov;34(3):451-6. doi: 10.1016/j.reprotox.2012.04.013. Epub 2012 May 5. at http://www.ncbi.nlm.nih.gov/pubmed/22569275 When effects of both prenatal and breast milk exposures to PCBs were considered, only “breast milk exposure to PCB 153 appears to be associated with decrements in motor development.”
-- To see four other studies that found postnatal effects of PCBs, see Section 3, cont. For additional studies finding associations of postnatal effects of PCBs when grouped together with dioxins, see the next section. Also see the Schantz et al., 2003 study in the dose response section, for effects of PCBs on learning and memory in adults.
Dioxins, often together with their chemical relatives, PCBs:
-- A Japanese study (Nagayama et al.) entitled, “Postnatal exposure to chlorinated dioxins and related chemicals on thyroid hormone status in Japanese breast-fed infants,” is of interest. Estimated intakes of dioxins and related chemicals in breast milk “significantly and negatively correlated” with the levels of thyroid hormones in the blood of breast-fed babies.44 This should be read while aware that thyroid hormones are important to development of the brain, specifically to the development taking place at a particular time47 (including cell proliferation -- see p.1). Also note that human milk is typically over 100 times higher in dioxin than formula, at initiation of breastfeeding (see Sect. 2, cont.).
-- An article in Environmental Health Perspectives (Porterfield, 1994) discusses effects of “PCB-dioxin exposure during the “critical period’ of brain development,” which the author considers to continue into an infant’s second year. Quoting, “Exposure of the developing brain both to hypothyroidism and PCB-dioxin (during the prenatal-to-early-postnatal period of brain development) have been shown to impair memory and learning.” The author’s concern was with effects even of “very low levels of these compounds -- levels below those generally recognized as toxic.”43
*-- Huisman et al., Perinatal exposure to polychlorinated biphenyls and dioxins and its effect on neonatal neurological development, Elsevier, Early Human Development, 41 (1995)111-127, at http://www.sciencedirect.com/science/article/pii/037837829401611R This Dutch study of 418 mother-infant pairs found that prenatal exposure to dioxins and PCBs did not show a correlation with postnatal neurological optimality, whereas “only breast-fed children who were perinatally exposed to higher dioxin, mono-ortho PCB, di-ortho PCB and total PCB/dioxin TEQ values showed a reduced neonatal neurological optimality.”
*-- Jusko et al., Pre- and Postnatal Polychlorinated Biphenyl Concentrations and Longitudinal Measures of Thymus Volume in Infants Environ Health Perspect. 2012 April; 120(4): 595–600. PMCID: PMC3339462. doi: 10.1289/ehp.1104229 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339462/
In this study supported by both the NIH and the European Commission, the authors stated that “TCDD (dioxin) and (the related chemical) dioxin-like PCBs have well-established effects on the immune system, one of which is thymic atrophy, an outcome observed in all species evaluated after TCDD exposure.” (The thymus “is necessary in early life for the normal development of immunologic function.” (Farlex Partner Medical Dictionary)) In their study of over 900 Slovakian mother-infant pairs, these investigators observed that maternal PCB concentration (therefore prenatal exposure of the infant) had no correlation with the size of the thymus at 6 or 16 months of age; but the infant’s PCB concentration at 6 months of age was associated with a significant decrease in the size of the thymus at that age. The effect of PCBs in reducing the size of the thymus at the 6-month point was so substantial (in relation to the effect associated with prenatal exposure to PCBs) that the authors concluded that their “results suggest that 6 months of age is … the period of greatest sensitivity to PCBs.” They pointed out that this finding of distinctly postnatal sensitivity of the thymus to toxins was also observed in other studies. Being aware of the special early-postnatal vulnerability of this gland that is necessary for development of immunological function, also note that PCB levels in children who had been breastfed for at least 12 weeks were found to be still over twice as high as in bottle-fed children even at 7 years of age. (This is stated together with other relevant evidence and authoritative sources in Section 1.a of www.breastfeeding-toxins.info, and also see the chart at the beginning of Section 2, cont., above.) So the 6-month postnatal PCB levels in breastfed children appear to be basically attributable to breastfeeding exposures, and therefore the PCB concentrations at 6 months that were associated with reduction in size of the thymus should also be attributable to breastfeeding.
*For another study by Jusko et al. finding harmful effects of postnatal but not prenatal exposure to developmental toxins, see Figure 4 and accompanying text at http://www.breastfeeding-vs-formula.info.
-- A 2007 study, by a Korean/American/Spanish research team (Lee et al.), of associations between toxin levels in children aged 12-15 and neurological disorders is especially significant in indicating apparent major effects of postnatal background exposures at an age that reveals long-term outcomes that are not detectable in studies of young children. (Almost all studies of effects of developmental toxins are of young children, often too young to reliably indicate long-term effects.). This study, using data from U.S. National Health and Nutrition Examination Survey (NHANES) 1999–2000, was apparently the only study that has been carried out on the association between background exposure to POPs (including dioxins) and clinically significant developmental disorders, such as learning disability or attention deficit disorder, among children from a general population. The authors found dramatically increased odds of the children’s having these disorders if they had detectable levels of dioxins or furans. The average odds ratio of having learning disability for those with detectable levels of dioxins/furans, compared with those without detectable levels, was 2.33 (that is, a 133% increased likelihood); and the average odds ratio of having attention deficit disorder for those with detectable levels of dioxins/furans, compared with those without detectable levels, was 3.02 (three times as likely).47a This study should be seen in combination with (a) the finding in a 2011 study by 13 scientists that dioxin levels were still twice as high in breastfed as in formula-fed young men even at ages 18 to 26 (see the Mocarelli et al. study below), and (b) the determination by a two-researcher team headed by an EPA senior scientist (citing five other studies with compatible findings) indicating that accumulated exposure to dioxins was expected to still be twice as high among children breastfed for six or more months as among non-breastfed children at ten years of age.47b It is reasonable to conclude (from these studies and from other information47c) that breastfeeding is by far the principal determinant of the extent of a typical developing child’s dioxin exposure. Note that increased dioxin levels were found in the above study to be linked with greatly increased rates of learning disability and attention deficit disorder, at ages sufficiently advanced to indicate long-term effects.
*-- Mocarelli et al., Perinatal Exposure to Low Doses of Dioxin Can Permanently Impair Human Semen Quality, Environ Health Perspect. May 2011; 119(5): 713–718. Published online Jan 24, 2011. doi: 10.1289/ehp.1002134 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3094426/ In this 2011 study, by 13 scientists, it was determined that the median levels of dioxins in breastfed infants were doubled within 4-5 months after birth, compared with levels in formula-fed infants that were reduced by half in that same period of time; after those infants had grown to ages ranging from 18 to 26, average dioxin concentrations were still twice as high in the breastfed young men as in those who had been formula fed. Breastfed sons born to mothers who had received “modest” increases of dioxin exposure had greatly decreased sperm concentrations compared with the breastfed comparison group as well as compared with the formula-fed groups. By contrast, sperm concentrations of the formula-fed exposed and comparison groups were not significantly different from each other. (Note that this was essentially an indication of the impact of breastfeeding, a postnatal exposure, and showing that the prenatal exposures of the mothers to the same toxins had no adverse effects on the children in the absence of breastfeeding.) It should be noted that reproductive function was all that this study was investigating; bear in mind that testosterone is also known to be important to development of the brain.
A 2009 study (Larssona et al.) concluded, “our study confirms that prenatal smoking and smoking during the child's first year of life can be coupled to ASD (Autism Spectrum Disorders).”69 This should be seen together with the finding of a 1998 study of 330 mother-infant pairs (Mascola et al.) that "breast-fed infants of smoking mothers have urine cotinine levels 10-fold higher than bottle-fed infants whose mothers smoke."70 (Cotinine is a marker for smoke exposure) The Larssona study supports a link between autism and a specifically early-postnatal exposure. The Mascola study provides additional confirmation that lactation is a highly efficient mechanism for taking in environmental toxins in moderate doses and transferring them to infants in concentrated form during the critical early-postnatal period; and those toxins have been closely linked with ASD.
* Day et al., Effects of prenatal tobacco exposure on preschoolers’ behavior. J Dev Behav Pediatr 2000;21(3):180–8. at http://www.ncbi.nlm.nih.gov/pubmed/10883878 This study indicated that postnatal (not prenatal) exposure predicted attention problems in 3-year-old children. As noted in the previous paragraph, children with by far the greatest postnatal exposure to effects of maternal smoking are breastfed children. (Note: this study did find some effects of prenatal smoking, but no effects related to attention)
Already cited in Section 2, cont. were studies finding major early-postnatal increases in mercury levels in breastfed infants as opposed to bottle-fed infants, which should be seen together with knowledge of the special postnatal vulnerability of the brain to mercury (see Section 1, cont.). Remember the study dealing with serious effects of specifically early-postnatal exposures to mercury (the Grandjean study that was the source of the “attenuated growth” chart on page 3). At least four studies have found high levels of mercury in those diagnosed with autism,70f in addition to the studies in the “heavy metals” section below. Other studies also have measured maternal mercury at time of birth or during pregnancy, and found poorer cognitive test scores later in children who had had those higher mercury exposures; the authors typically referred to those exposures as “prenatal,” but no reason was provided to think that those mercury levels would not have been good indications of early-postnatal exposures in breast milk.70c, 60b 70d
*A Taiwanese study of three-year-olds (His et al.) distinguished between prenatal and postnatal effects of methylmercury, and found no significant effects of prenatal exposure, but did find apparent effects of postnatal mercury levels, with those levels negatively correlating with scores in a test of expressive language.70b (Bear in mind that language impairment is one of the traits of autism.)
* In tests of neuromotor functions in a study (Despres et al.), current mercury levels, but not pre-natal, were associated with increased action tremor amplitude at 4–6 years of age.60d
* “In the Faroes, delays in transmission of auditory brain signals in 14-year-old birth cohort members were associated with each child's recent mercury exposure from fish in their own diets, not with their prenatal mercury exposures (Murata et al., 2004).” That was as stated in Grandjean et al., Neurotoxicity from prenatal and postnatal exposure to methylmercury, Neurotoxicol Teratol. 2014 May-Jun; 43: 39–44. PMCID: PMC4066386 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066386/
-- At least one other study also found adverse cognitive effects of postnatal methylmercury levels, measured well past the prenatal period, on toddlers.60c “After adjustment for fish intake, T-Hg levels (in hair) > or =1microg/g were associated with decrements in the general cognitive (-6.6 points), memory (-8.4 points), and verbal (-7.5 points) MSCA scores.”
-- A study with mice provided additional support for seeing the toxic effects of methylmercury exposure to be greater in the later period of brain development (specifically in the cerebellum, and early-postnatally) rather than in the earlier period.(70g)
* A 2014 study found that “the results for the Bender reproduction score suggest that postnatal methylmercury exposure may affect visuospatial memory, and that the effect in regard to this function may be stronger for exposures at late preschool age than for prenatal exposures.” (Grandjean et al., Neurotoxicity from prenatal and postnatal exposure to methylmercury, Neurotoxicol Teratol. 2014 May-Jun; 43: 39–44. PMCID: PMC4066386 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066386/)
Various studies have found mixed or no effects of postnatal exposure to mercury, but apparently all of those either measured mercury levels in children at ages past the critical early-postnatal period of brain development, or else they assessed only effects of ethylmercury (used in Thimerosal), which is just one of a number of different species of mercury. (See “Examples of how a misconception about prenatal vs. postnatal exposures is formed and propogated” in Appendix B.)
Some studies have found harmful effects on adults of low-dose exposure to mercury,70h, 70i, 70k and the Mocarelli study above found harmful effects on older male children of low-dose exposure to mercury.
To summarize about mercury effects: It appears to be generally accepted that mercury, especially methylmercury, is a neurodevelopmental toxin. It is widely believed to mainly act prenatally, although there have been major studies (in Seychelles, notably) that found no effects from known prenatal exposures to mercury.(70m) The studies that have found effects associated with what are assumed to be prenatal exposures have not distinguished those exposures from lactational exposures that would have been closely related to the prenatal or time-of-birth measurements of mercury; it is entirely possible that most or all of the effects of those “prenatal” mercury levels were as a result of lactational transfer of toxins that were accumulating prenatally. Apparently most or all of the studies that have found no effects of “postnatal” exposures took measurements well after the critical early-postnatal period. (See “Examples.) And it appears that all of the studies that took their measurements in the early postnatal period did find adverse neurological effects of mercury exposure. (See above)
Phthalates: To appreciate how the next studies relate to specifically early-postnatal exposures to developmental toxins, note that
(b) phthalates “interfere with how testosterone is made,” 70e (also see the Main and Meeker studies below), and
(c) phthalate concentrations in human milk are high, far higher than those in infant formula or cows’ milk. Two separate studies (with 130 and 36 milk samples tested) each found six different forms of phthalates present in 100% of the breast milk samples;75, 76 by comparison, what was apparently the most thorough study of phthalates in cows’ milk (7 samples tested) and infant formula (10 samples) detected only two forms of phthalates present; those two forms were found in lower average concentrations in cows’ milk and formula than were found in breast milk.77
-- Main et al., Human Breast Milk Contamination with Phthalates and Alterations of Endogenous Reproductive Hormones in Infants Three Months of Age, Environ Health Perspect. 2006 February; 114(2): 270–276. at http://www.ncbi.nlm.nih.gov/pubmed/16451866 This study reported significant decreases in free testosterone and Leydig cell function in 3 month-old boys in relation to phthalates in maternal breast milk. (Leydig cells are important to production of testosterone, which in turn is important to brain development.24,25)
-- Meeker, Exposure to Environmental Endocrine Disruptors and Child Development JAMA Pediatrics, Oct 2012, Vol 166, No. 10 at http://archpedi.jamanetwork.com/article.aspx?articleid=1171946 “Several phthalates are antiandrogenic… In human studies of adults, phthalates have been related to decreases in sex steroid and thyroid hormone levels, poor sperm quality….” This should be seen together with the recognition that sex steroids are important to development of the brain24, 25 and that brain development is sensitive to deficits of thyroid hormones during the specific stage of development that is taking place at the time, including cell proliferation.47 See Figure 1 about the cell proliferation that takes place postnatally in the brain.
-- Larsson M et al., Associations between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age. Neurotoxicology 30: 822-831. (2009) This large Swedish epidemiological study observed that the presence of PVC flooring material in the home, when the child was 1–3 years of age, was associated with ASD five years later.80 (PVC typically contains phthalates.81)
-- Kim, BN et al., Phthalates exposure and attention-deficit/hyperactivity disorder in school-age children, Biol Psychiatry, 2009 Nov 15;66(10):958-63. doi: 10.1016/j.biopsych.2009.07.034. Epub 2009 Sep 12. at http://www.ncbi.nlm.nih.gov/pubmed/19748073 “The present study showed a strong positive association between phthalate metabolites in urine (of the children) and symptoms of ADHD among school-age children.
-- Cho SC et al.,Relationship between environmental phthalate exposure and the intelligence of school-age children, Environ Health Perspect. 2010 Jul;118(7):1027-32. doi: 10.1289/ehp.0901376. Epub 2010 Mar 1 at
http://www.ncbi.nlm.nih.gov/pubmed/20194078 This study of 667 children at nine elementary schools in five South Korean cities arrived at a finding of an inverse relationship between phthalate metabolites and IQ scores.
The focus of this article is on cognitive development, but any environmental exposure (including the distinctly early-postnatal exposure to phthalates described here) that reduces testosterone production should be of concern for other reasons also. Reproductive effects should obviously be of concern, especially in an age when most developed countries have negative population growth; the U.S. is barely in the positive growth range because of births to immigrant women; it has had a recent average of 1.1 children born per married, native-born American woman,84, requiring considerable expenditure on assisted reproductive technologies in reaching even that low number. According to a 2011 study, “There is now a general consensus that human sperm quality has declined over time in different areas of the world (Auger et al. 1995; Jørgensen et al. 2001; Swan et al. 2003), especially in younger men (López-Teijòn et al. 2008; Zheng et al. 1997), with indications of concurrent male sub- or infertility (Bonde et al. 1998; Paasch et al. 2008; Zheng et al. 1997).”(81a) Note the phrase “especially in younger men,” and consider the significance of that in relation to the major increases in breastfeeding during the last few decades.
* Schnaas et al., Temporal pattern in the effect of postnatal blood lead level on intellectual development of young children. Neurotoxicol Teratol. 2000;22:805–810, at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1247191/#b70-ehp0112-000987. This study found strong effects of postnatal lead exposure on mental development but no effects of prenatal exposure to lead.
* Huang et al., Childhood blood lead levels and intellectual development after ban of leaded gasoline in Taiwan: a 9-year prospective study. Environ Int. 2012 Apr;40:88-96. doi: 10.1016/j.envint.2011.10.011. Epub 2012 Jan 13. at http://www.ncbi.nlm.nih.gov/pubmed/22280932. This study found that postnatal exposure to lead was associated with decreased IQ and delayed neurological development, but prenatal exposures had no effect.
* * * * Lamphear et al., Cognitive deficits associated with blood lead concentrations <10 microg/dL in US children and adolescents, Public Health Rep. 2000 Nov-Dec; 115(6): 521–529. at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1308622/ This year 2000 study cited five other studies in support of its statement that “prospective studies have reported that the detrimental effects of prenatal lead exposure on intelligence appear to be attenuated in later childhood, whereas postnatal lead exposure has been associated with persistent effects of greater magnitude.”
* A 2015 study, definitely not included among those referred to above, found that prenatal exposures to lead had to be greater in order to have significant adverse effects, compared with well-reported findings of postnatal effects of low lead exposures: Jacobson et al., Relation of Prenatal Methylmercury Exposure from Environmental Sources to Childhood IQ, Environ Health Perspect; DOI:10.1289/ehp.1408554 , Volume 123 | Issue 8 | August 2015 at http://ehp.niehs.nih.gov/1408554/
The next studies are relevant here due to the obvious fact that breastfeeding is a postnatal exposure:
-- Ettinger et al. found that “a 1-μg/L increase in breast milk lead increased infant blood lead… among infants exclusively breastfed in the previous month (2.2 μg/dL) compared with breastfeeding infants who were not exclusively breastfed in the preceding month (1.1 μg/dL)”. (Ettinger et al. (2014), Maternal Blood, Plasma, and Breast Milk Lead: Lactational Transfer and Contribution to Infant Exposure, Environ Health Perspect; DOI:10.1289/ehp.1307187 at http://ehp.niehs.nih.gov/1307187\
-- Also from the above source, “a study of breastfeeding duration and infant blood lead reported that longer breastfeeding was associated with higher infant lead concentrations in three countries, in three different decades, in settings with differing breastfeeding patterns, environmental lead sources, and infant lead levels (Lozoff et al. 2009).“
At least one study has found effects of postnatal lead exposure that appear to be greater than prenatal exposure, in the same region.82
Aside from the above studies finding effects of lead to be mainly or only related to postnatal exposure, there are too many studies to mention that found adverse effects of lead exposure in low concentrations in children, with ample reason to see the exposures to have been basically postnatal.
It is also instructive to look at the history of treatment of toxicity of lead. Lead’s toxicity has been known for centuries, so we should have been alert to its dangers when putting it into a substance (gasoline) that could have been predicted to result in its inhalation by vulnerable children and child-bearing women everywhere. And there were clear signs of neurological toxicity of tetraethyl lead soon after it went into gasoline in the 1920’s. But it was pumped massively into our air for a half century, with no apparent complaints from the medical community, before it was banned from gasoline. In his article, “Vulnerability of Children and the Developing Brain to Neurotoxic Hazards,” a leading expert in this field, Bernard Weiss, says, “We have only begun to grasp the breadth of challenges that chemical contamination of the environment poses to the developing brain…. (Detecting effects of low-dose environmental chemicals) proved elusive because they were subtle enough not to be immediately apparent; moreover, we simply did not understand how to ask the proper questions about their toxicity. Recall the struggle to document the dangers of smoking.” 83
*Studies marked above with asterisks found effects of postnatal exposures to toxins while finding less or no effects of prenatal exposures to the same toxins
Autism and other Pervasive Development Disorder:
Remember the four studies (mentioned in Section 6 ) relating breastfeeding to autism, including the one by a highly-published scientist who concluded about apparent effects of a distinctly postnatal exposure, based on a study of all 50 states and 51 U.S. counties, that “breast-feeding shows a direct epidemiological relationship to autism," with the relationship increasing in a dose-response relationship with the duration of breastfeeding.8 Whether this correlation is thought to be related to nutritional deficiencies in the feeding or to the presence of developmental toxins in the feeding, in either case it appears to be an early-postnatal exposure that should be the basis for concern.
According to a major 2014 review article, twenty-one studies examined estimated childhood exposures to toxicants and ASD, with 19 (90%) reporting a positive association. The toxicants most implicated included pesticides, toxic waste sites, phthalates, air pollutants and heavy metals. (Rossignol et al., Environmental toxicants and autism spectrum disorders: a systematic review, Transl Psychiatry. 2014 Feb; 4(2): e360. PMCID: PMC3944636 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944636/)
*-- PDD (pervasive development disorder), the diagnostic category under which autism falls, was found in a study (Eskenazi et al., 2007) to be 70% more likely among children with postnatal concentrations of urinary metabolites of organophosphate pesticides. The statistical significance of this finding was also determined to be greater than the (borderline) statistical significance of the finding of associations of a child’s PDD with prenatal concentrations of those same metabolites.(83a)
-- A laboratory experiment (Curtis et al.) with prairie voles (which have similarities to humans in social interaction) found that chronic ingestion of mercury in environmentally-relevant doses substantially reduced social contact by male voles when they were given a choice between isolation or contact with an unfamiliar same-sex mole. The effects of metals ingestion were specific to males: no effects of metals exposure were seen in females. The authors concluded, “thus, an ecologically relevant stimulus, metals ingestion, produced two of the hallmark characteristics of autism – social avoidance and a male-oriented bias…. One of the more striking results in the present study was the robust and consistent difference in the effects of metals ingestion between male and female voles.”(83b) Clearly, the effects found were of postnatal exposures.
*-- A 2007 study found six times the normal risk of ASD among children whose mothers at time of birth lived near organochlorine pesticide application areas in California. “ASD risk increased with the poundage of organochlorine applied and decreased with distance from field sites.” (The study carried out an analysis of 465 children with ASDs along with 15 control subjects per case.)(83c) A subsequent, associated study found, by means of thorough statistical analysis of the above study’s data and of state records of pesticide applications, that in addition to a period of vulnerability to the toxins during gestation, there was an even stronger period of vulnerability during the first year after birth. The likelihood that this finding would have been a result of chance alone was .003, or 3 out of 1000; that was a four-times-lower likelihood of chance occurrence than applied to the finding of a gestational period of vulnerability (.013)(83d). As described with considerable evidence at www.autism-studies.info, the avenue by which the infants would have received their greatest exposures to pesticides was via breastfeeding.
It should be noted that the authors of the above study indicated that they had been surprised that there turned out to be a postnatal period of vulnerability to the toxins. Without the substantial, unusual, additional investigation by means of the second study above, the first study would probably have remained as yet another of the many studies that have found effects of allegedly “prenatal” exposures.
*-- Metabolites (DEs) of certain types of pesticides were found to be associated with pervasive development disorder postnatally but not prenatally.83e
Also see the Larsson study in the Phthalates section above, regarding apparent autism-related associations of dermal exposure of infants to that toxin in a flooring material.
A German/Egyptian research team (Blaurock-Busch et al.) summarized the results of seven other studies all of which were in agreement with their own findings, to the effect that “heavy metals, especially lead, play a role in the development of ASD. The various studies measured heavy metals in the hair, blood and urine in children with autism. Given the short half-lives of lead and mercury in blood,79 and the fact that the measurements were taken after the children were old enough to be diagnosed with autism, it is unlikely that the associations detected were with anything other than essentially postnatal exposures to the metals. (Note that none of the studies below are repetitions of the mercury studies referred to earlier.) “As early as 1976, Cohen et al. noted elevated blood lead levels in ASD children. In 1998 Kumar et al. confirmed elevated blood lead levels in ASD children. Lonsdale et al. observed increases in urinary concentrations of cadmium, nickel, and lead among children with pervasive mental disorder. AL-Ayadhi in his evaluation of Riyadh children found significantly higher levels of toxic heavy metals mercury, lead, arsenic, antimony and cadmium in the hair of children with autistic spectrum disorder as compared to normal children. A study of Kuwaiti children (Hassanien et al.) found significant elevations of environmental metals in children with autism. Mercury levels of the autistic group were 15 times higher than in the control group. Bernard et al. noted that autistic children who were postnatally poisoned developed articulation problems, from slow, slurred word production to an inability to generate meaningful speech. Communication and learning problems are common among ASD patients. Brockel and Cory-Slechta found high lead levels to be associated with negative effects on childhood development, cognitive ability, learning and behavioral disabilities, attention deficit hyperactivity disorder, impulsivity, and inability to inhibit inappropriate responding. Our data supports this.”80 (See the study at 80 for the studies cited above.)
Another review, published in 2014, reported that seven studies found a dose-effect relationship between heavy metal concentrations from various tissues/body fluids in children and ASD.80a
Immunological problems, which are related to autism: The above studies deal with apparent neurological and related effects of toxins ingested by infants in the early postnatal period. It should be mentioned that there has been increasing evidence of connections between immunological development and neurological development; one expert team pointed out “the tight connection between development of the immune system and that of the central nervous system,” and also the plausibility that “disruption of critical events in immune development may play a role in neurobehavioural disorders.“77 In that regard, it is relevant that over 30 studies have found apparent adverse effects of (the distinctly early-postnatal) breastfeeding on risk of immunity-related diseases (asthma, allergies and diabetes); those studies can be found at www.breastfeeding-studies.info, Sections 2.c.1 and 2.c.2; seven of those studies found adverse dose-response relationships of allergies with breastfeeding (Section 2.a at above link).
*-- A 2015 study found associations between risk of allergies and exposure to traffic-related air pollution during the first year of life but not to exposures during gestation. (Sbihi et al., Perinatal Exposure to Traffic-Related Air Pollution and Atopy at 1 Year of Age in a Multi-Center Canadian Birth Cohort Study, http://dx.doi.org/10.1289/ehp.1408700, Advance Publication: 31 March 2015. at http://ehp.niehs.nih.gov/wp-content/uploads/advpub/2015/3/ehp.1408700.acco.pdf)
BPA, related to asthma, adiposity, attention, behavior, and learning:
*-- The following 2013 study found that prenatal exposure to BPA was not associated with increased asthma in the children in later years, but postnatal exposures measured at three different ages were associated with increased asthma: Donohue et al., Prenatal and postnatal bisphenol A exposure and asthma development among inner-city children, J Allergy Clin Immunol. 2013 Mar; 131(3): 736–742. doi: 10.1016/j.jaci.2012.12.1573 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3643970/
*-- The following 2013 study found that prenatal exposure to BPA was not associated with increased adiposity in childhood, but postnatal exposures were associated with increased adiposity in childhood: Harley et al., Prenatal and Postnatal Bisphenol A Exposure and Body Mass Index in Childhood in the CHAMACOS Cohort, volume 121 | number 4 | April 2013 • Environmental Health Perspectives, at http://stacks.cdc.gov/view/cdc/13443/
-- A 2014 review article by a team of four scientists reported that “In cross-sectional analyses, BPA concentrations in childhood spot urine are associated with increased internalizing and attention problems in boys and externalizing and conduct problems in girls at age seven. Furthermore, a study observing children ages 8–11 found a positive association between BPA levels in urine and anxiety and depression…. a negative association was found between urinary BPA concentration and total learning quotient using the Learning Disability Evaluation Scale…. it is clear that perinatal and childhood BPA exposure may alter behavior, perhaps in a sexually dimorphic manner, which agrees with the results of animal studies.” (Mileva et al., Bisphenol-A: Epigenetic Reprogramming and Effects on Reproduction and Behavior, Int J Environ Res Public Health. 2014 Jul; 11(7): 7537–7561. Published online 2014 Jul 22. doi: 10.3390/ijerph110707537 PMCID: PMC4113893 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113893/)
-- The following study found effects of background exposures to PCBs combined with PBDEs in reduced scores on measures of verbal memory and learning of adults: Fitzgerald and six others, Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and neuropsychological status among older adults in New York. Neurotoxicology. 2012 Jan;33(1):8-15. doi: 10.1016/j.neuro.2011.10.011. Epub 2011 Nov 6.
Appendix B: More on why some studies did not report harmful effects of postnatal exposures to developmental toxins: Researchers’ biases, distorted findings reported, and publication bias.
Pertinent comments on this topic are provided by Dr. John Ioannidis, chair in Disease Prevention at Stanford University School of Medicine and adjunct professor at Harvard School of Public Health, as follows: “Claimed research findings may often be simply accurate measures of the prevailing bias.” There can be little doubt that there is currently a prevailing bias in favor of promoting breastfeeding,54 which would make people tend to overlook effects of the high (early-postnatal) exposures of infants to toxins in breast milk. Dr. Ioannidis continues, “false findings may be the majority or even the vast majority of published research claims,” resulting from (among other things) “various combinations of selective or distorted reporting of the results.”55 (Note that the above-quoted statements were made by a highly-placed doctor and scientist, not by a critic from outside those professions.)
Publication bias, a recognized problem in scientific research, would apply to (a) biases among publishers and peer reviewers who would tend to favor reports that are in line with prevailing views and with what most readers are expected to want to read, and (b) disinclination of researchers to try to have findings published that they suspect will be unfavorably received by most of their colleagues and by officials who control research grant money. (see 54) Many studies have been done of the relationship between prenatal toxic exposures and child development, without reporting about effects of early-postnatal exposures; considering the known continuation of neurological development postnatally and the relative ease of taking breastfeeding histories, it is probably a reflection of the general groupthink that early-postnatal exposure is rarely assessed (or, more precisely, it is rarely reported).
Dr. Herbert L. Needleman (member of Institute of Medicine of the National Academy of Sciences, recipient of many science awards, author of over 80 publications, and pioneer in establishing toxicity of lead in low doses)55c provides comments along lines similar to those of Dr. Ioannidis, when he refers to the effects of “long-held social myths” and “prevailing beliefs” in preventing scientists from reaching valid conclusions about effects of low-level environmental toxins; he talks of those problems in relation to the half-century delay after strong evidence of toxicity of tetraethyl lead was observed before it was banned in gasoline.55a He raises an interesting question relating that delay to the many other toxins that have been added to contemporary environments in recent decades, long-term effects of most of which we know even less about than we knew about lead in the 1920’s: “Given the omnipresence of these new toxicants, and the categorical impossibility of achieving causal proof of their toxicity, what should be done? If society awaits causal proof of the toxicity of an agent, millions of people will have paid the price of exposure.” Dr. Needleman’s question is particularly relevant to the agents ingested by those whose entire lives are most vulnerable to the toxins’ effects: developing infants; that is especially the case since over 350 different contaminants have been found in human milk,55b in addition to the known very large excesses of certain developmental toxins in breast milk in comparison with recognized safe levels. (see Section 2)
Examples of how a misconception about prenatal vs. postnatal exposures is formed and propogated:
-- Exposures tested too late to be relevant to the critical early-postnatal period. It is apparently typical that, when studies are purportedly investigating effects of postnatal exposures to mercury, they conduct their exposure assessments at times that are far removed from the period of the infant’s greatest vulnerability to toxins. A Danish study (Debes et al.) concluded with the finding, “Postnatal exposure to methylmercury had no discernible effect.”59 Most readers would assume that this statement relates to a child’s general postnatal vulnerability to toxins. But the study’s measurements of mercury levels in the children were carried out at age 14; in relation to that, remember from earlier (a) the early-postnatal critical period of vulnerability, (b) the findings that an infant’s mercury levels can be doubled or tripled in the first year of life by a widely-used type of early-postnatal feeding (see Section 2, cont.), and (c) the short half-life of mercury in the body (see Section 5.d). So the finding of “no discernible effect” of “postnatal” exposure, based on exposure at age 14, was quite misleading to the general reader.
-- Misleading, selective reviewing of other research: An example is a review about “Postnatal Exposure to Methyl Mercury” from fish consumption, by Myers et al. In a chart summarizing “associations between postnatal MeHg (methylmercury) exposure and developmental endpoints,” the above statement about “no discernible effect” was merely quoted verbatim, making it appear that the Debes study’s measurements of mercury exposure at age 14 were a valid measure of a child’s postnatal vulnerability to mercury. In addition, the authors gave that statement extra prominence by repeating it in the concluding words of a paragraph, following descriptions of mixed effects of earlier testing of the same children; this gave the impression that the 14-year-old children’s results were a meaningful resolution of the mixed results of earlier testing. They said nothing to acknowledge that exposures at older ages may have little relevance to the critical early-postnatal period of vulnerability to neuro-developmental toxins.60 In addition, 11 of the 12 studies in the above-mentioned summary chart measured mercury levels in children aged 5 and older, in the process of telling about the presumed effects of “postnatal exposure” to mercury. (One study in which exposures were measured after age 5 was erroneously reported as having done evaluations at earlier ages.(60a)) The one study that measured early-postnatal exposure only assessed the apparent outcomes at age one, which was essentially meaningless in predicting the long-term consequences of that exposure. One year of age would be a good time to be measuring exposures, but is far too early to pay significant attention to outcomes.
-- Ignoring strongly-conflicting research: At minimum, such conflicting research (ignored in the above-discussed Myers et al. review) should have included the Grandjean et al. study published six years earlier,22 which was the source of the “attenuated growth” chart shown on page 3; that found very substantial effects of early-postnatal methyl-mercury exposure from seafood consumption (ingested via lactation). If Myers et al., had considered this study not to be relevant to their analysis for some reason, they should at least have referred to it and explained why they omitted it.
A reasonable explanation for research such as the above, on the part of a large team of scientists and with the apparent acquiescence of their peer reviewers, is that there is a general bias against belief in existence of postnatal effects of developmental toxins. Remember the statements by a prominent scientist and doctor quoted earlier, about prevalence of “selective or distorted reporting,” and saying that “Claimed research findings may often be simply accurate measures of the prevailing bias.”
In line with the above, it should be pointed out that it appears to be normal for researchers to consider measurements of mercury levels in mothers at time of birth to indicate prenatal exposure of the infant, while providing no recognition that those measurements would also correlate with postnatal infant exposures, via breastfeeding. They may assess mercury levels far past the critical early-postnatal period, and those are the only exposures they offer to represent “postnatal” exposures of the child.60b
Of great significance (in the charts in Section 3 cont.) is the apparent fact that exposure to mercury seems to be associated with generally favorable effects on certain test scores of females. This phenomenon is important regarding how test results in studies of effects of toxins should be reported and interpreted. It is apparent that, in the case of background exposures to at least one major developmental toxin, harm is being done to male children, but that harm is generally going unnoticed because favorable effects on females mostly obscure the adverse effects on males, as the results normally appear (that is, not reported separately by gender).
Evidence that suggests opposing gender-related effects of toxins also appears in another study that shows results for male children and female children separately, a 2013 study by nine U.S. scientists (Roberts et al., “Perinatal Air Pollutant Exposures and Autism Spectrum Disorder in the Children of Nurses’ Health Study II Participants”). This large study investigated associations between autism diagnoses and exposures at time of birth to atmospheric pollutants, specifically comparing results between the top quintile of exposures and the bottom quintile. The results were shown separately for boys and girls, indicating odds ratios for having autism associated with high exposures to mercury and nickel, compared to associations with low exposures to those same metals; the odds ratios for autism associated with those two metals were 1.6 and 1.9 for boys, compared with 0.5 and 0.7 for girls.(87) So for these two heavy metals, girls’ outcomes were substantially better than average while boys’ outcomes were substantially worse; those opposite results would cause the adverse effects on the vulnerable males to be greatly obscured, as the results are reported in a typical study.
Combining the above with the study findings shown in the chart in Section 3 cont., can anybody see a reason why this is not good evidence to support the following hypothesis:
that neurodevelopmental harm is being caused to male children by toxins, but harmful effects of those toxins are sometimes going unreported because favorable effects on females largely cancel out the adverse effects on males, as presented in normal reporting?
If anybody can think of an alternative explanation for what is happening, please write to firstname.lastname@example.org for inclusion here.
Aside from effects’ going in opposite directions for males versus females, there is also evidence that environmental toxins can have serious adverse effects on one sex while having little or no effect on the other sex. Reporting that does not reveal gender differences in such cases is likely to see only insignificant effects in combined results, while the effects on one sex may actually be very significant. For a study that found far worse cognitive effects of DDT on girls than on boys, see Ribas-Fito et al., In Utero Exposure to Background Concentrations of DDT and Cognitive Functioning among Preschoolers, Oxford Journals, American Journal of Epidemiology, Volume 164 Issue 10 Pp. 955-962. at http://aje.oxfordjournals.org/content/164/10/955.full
For a study that found adverse effects of an organochlorine pesticide on fine motor skills of boys but not of girls, see Boucher et al., Exposure to an organochlorine pesticide (chlordecone) and development of 18-month-old infants, NeuroToxicology, Volume 35, March 2013, Pages 162–168, at http://www.sciencedirect.com/science/article/pii/S0161813X13000193
One study finding greater harm to male children than to female children by pesticides provided the following suggested biological rationales: “Several factors may contribute to the differential vulnerability to CPF by sex. One potential explanation is CPF’s role as an endocrine disrupter. CPF has been shown to have anti-androgenic effects reducing serum testosterone levels in rats (Kang, et al., 2004). Male rats have a higher rate of hepatic activation of the CPF oxon, the metabolite that inhibits acetylcholinesterase AcTH, as well as more rapid detoxification of the CPF oxon. Inhibition of AcTH is noted as the mechanism of systemic toxicity for chlorpyrifos (Smegal, 2000). However, sexual differences in the activities of these enzymes that carry out the functions generally do not emerge until puberty. Further, the effects observed occur at levels well below those required to inhibit AcTH. Males have a slower rate of cortical development than females, making the male brain susceptible to insult for a longer period (Taylor, 1969).” (Horton et al., Does the home environment and the sex of the child modify the adverse effects of prenatal exposure to chlorpyrifos on child working memory? Neurotoxicol Teratol. 2012 Sep-Oct; 34(5): 534–541. Published online 2012 Jul 21. doi: 10.1016/j.ntt.2012.07.004 PMCID: PMC3901426 NIHMSID: NIHMS504636, at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901426/)
For many more studies showing harmful effects of environmental toxins on males without similar effects on females, see Appendix G of www.child-disability.info.
1) Mendola P et al, Environmental factors associated with a spectrum of neurodevelopmental deficits, Ment Retard Dev Disabil Res Rev. 2002;8(3):188-97 at www.ncbi.nlm.nih.gov/pubmed/12216063; also see EPA’s 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD); CASRN 1746-01-6, Section 1.a.2, at http://www.epa.gov/iris/subst/1024.htm
2) Rice et al., Critical Periods of Vulnerability for the Developing Nervous System: Evidence from Humans and Animal Models, EPA National Center for Environmental Assessment, at www.ncbi.nlm.nih.gov/pmc/articles/PMC1637807
3) Jensen, A.A. et al, Chemical Contaminants in Human Milk, CRC Press, Inc., Boca Raton, Ann Arbor, Boston, 1991, p 15. This is fully compatible with the statement by two other experts as follows: “Persistent lipophilic substances, including specific pesticides and halogenated industrial compounds, such as PCBs, accumulate in maternal adipose tissue and are passed on to the infant via breast milk, resulting in infant exposure that exceeds the mother’s own exposure by 100-fold on the basis of bodyweight.” (Grandjean P, Landrigan PJ. Developmental neurotoxicity of industrial chemicals. Lancet. 2006;368:2167–2178
Other earlier research that is still cited decades later is compatible with this: Gallenberg et al., Transfer of persistent chemicals in milk. Drug Metab. Rev. 1989;21:277-317
This is also compatible with the very large differences between concentrations of toxins in breast milk and those in alternative infant feeding -- see Section 2, cont.
For a more recent study finding even more disproportionate ratios between organohalogens in breast milk versus those in cord tissue and cord serum, see Needham et al., Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues, Environ Sci Technol. Feb 1, 2011; 45(3): 1121–1126, at http://pubs.acs.org/doi/pdf/10.1021/es1019614, Table 2, finding weight-based concentrations of organohalagens to be over 30 times higher in human milk than in umbilical cord tissue.
3a) Eriksson et al., Polybrominated Diphenyl Ethers, A Group of Brominated Flame Retardants, Can Interact with Polychlorinated Biphenyls in Enhancing Developmental Neurobehavioral Defects at http://toxsci.oxfordjournals.org/content/94/2/302.full
3b) Exploration of Perinatal Pharmacokinetic Issues Contract No. 68-C-99-238, Task Order No. 13 Prepared for EPA by: Versar, Inc. EPA/630/R-01/004, Section 18.104.22.168, at www.epa.gov/raf/publications/pdfs/PPKFINAL.PDF
3c) P. Grandjean et al., Human Milk as a Source of Methylmercury Exposure in Infants, Environmental Health Perspectives, accepted Oct. 1993 www.ncbi.nlm.nih.gov/pmc/articles/PMC1567218/pdf with compatible results found in other studies: Marques RC, et al., Hair mercury in breast-fed infants exposed to thimerosal-preserved vaccines. Eur J Pediatr. 2007 Sep;166(9):935-41 at www.sarnet.org/lib/VaxHgBrazil1.pdf; the authors found that, during 6 months of breastfeeding, infants' hair-Hg increased 446%, 40% of which was from vaccinations. Also see reference 3b, above.
3d) Houtrow et al., Changing Trends of Childhood Disability, 2001–2011, Pediatrics Vol. 134 No. 3 September 1, 2014 at http://pediatrics.aappublications.org/content/134/3/530.abstract
5a) Zoeller et al., Timing of Thyroid Hormone Action in the Developing Brain: Clinical Observations and Experimental Findings, Journal of Neuroendocrinology, Volume 16, Issue 10, pages 809–818, October 2004 at http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2826.2004.01243.x/full
also “Thyroid Hormone Disruption: Dioxins Linked To Attention Deficit, Learning Problems,” Jam 13, 1998, Science Daily, http://www.sciencedaily.com/releases/1998/01/980113155609.htm;
also Costa et al., Developmental Neurotoxicity of Polybrominated Diphenyl Ether (PBDE) Flame Retardants, Neurotoxicology. 2007 November; 28(6): at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118052/; also Zhou et al., Developmental exposure to brominated diphenyl ethers results in thyroid hormone disruption, Toxicol Sci, 2002
5c) Boukhtouche et al., Induction of early Purkinje cell dendritic differentiation by thyroid hormone requires RORα, Neural Development 2010, 5:18 doi:10.1186/1749-8104-5-18 at http://www.neuraldevelopment.com/content/5/1/18
5d) Hauser et al., Resistance to Thyroid Hormone: Implications for Neurodevelopmental Research on the Effects of Thyroid Hormone Disruptors, Toxicol Ind Health January 1998 vol. 14 no. 1-2 85-101at http://tih.sagepub.com/content/14/1-2/85.abstract.
Also, “Thyroid Hormone Disruption: Dioxins Linked To Attention Deficit, Learning Problems,” Jan. 13, 1998, Science Daily, http://www.sciencedaily.com/releases/1998/01/980113155609.htm;
Also EPA statement in 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD); CASRN 1746-01-6 at http://www.epa.gov/iris/subst/1024.htm, from which the following is quoted: “For TCDD, the toxicological concern is… increased metabolism and clearance of the thyroid hormone, thyroxine (T4). Adequate levels of thyroid hormone are essential in the newborn and young infant as this is a period of active brain development (Zoeller and Rovet, 2004; Glinoer and Delange, 2000). Thyroid hormone disruption during pregnancy and in the neonatal period can lead to neurological deficiencies, particularly in the attention and memory domains (Oerbeck et al., 2005).”
5e) Brouwer et al., Interactions of Persistent Environmental Organohalogens With the Thyroid Hormone System: Mechanisms and Possible Consequences for Animal and Human Health, Toxicol Ind Health January 1998 vol. 14 no. 1-2 59-84 at http://tih.sagepub.com/content/14/1-2/59.abstract.
5f) Chen et al., Thyroid hormones in relation to lead, mercury, and cadmium exposure in the National Health and Nutrition Examination Survey, 2007-2008, Environ Health Perspect. 2013 Feb;121(2):181-6. doi: 10.1289/ehp.1205239. Epub 2012 Nov 15. at http://www.ncbi.nlm.nih.gov/pubmed/23164649
5g) NIH web page at http://www.nlm.nih.gov/medlineplus/ency/article/001193.htm
5h) U.S. ATSDR, Toxicological Profile for Mercury, p. 556, at http://www.atsdr.cdc.gov/toxprofiles/tp46.pdf#page=1&zoom=auto,-34,792
5k) Drexler et al., The mercury concentration in breast milk resulting from amalgam fillings and dietary habits, Environ Res. 1998 May;77(2):124-9. at http://www.ncbi.nlm.nih.gov/pubmed/9600805. another study also found evidence of excretion of mercury during breastfeeding. (Vahter, Longitudinal Study of Methylmercury and Inorganic Mercury in Blood and Urine of Pregnant and Lactating Women, as Well as in Umbilical Cord Blood, Environmental Research, Volume 84, Issue 2, October 2000, Pages 186–194
5m) Lok, E. 1983. The effect of weaning on blood, hair, fecal and urinary mercury after chronic ingestion of methylmercuric chloride by infant monkeys. Toxicology Letters, Volume 15, Issues 2–3, February 1983, Pages 147–152, abstract at www.sciencedirect.com/science/article/pii/0378427483902084
6) Exploration of Perinatal Pharmacokinetic Issues Contract No. 68-C-99-238, Task Order No. 13 Prepared for EPA by: Versar, Inc. EPA/630/R-01/004, Section 22.214.171.124, at www.epa.gov/raf/publications/pdfs/PPKFINAL.PDF
6a) National Research Council (U.S.). Committee on Toxicology, Recommendations for the Prevention of Lead Poisoning in Children, p. 19, at https://books.google.com https://books.google.com/books? The following direct link might work: id=15grAAAAYAAJ&printsec=frontcover&dq=Recommendations+for+the+Prevention+of+Lead+Poisoning+in+Children&hl=en&sa=X&ved=0CB4Q6AEwAGoVChMI06yW25q2xwIVjQqSCh2dsQ2G#v=onepage&q=Recommendations%20for%20the%20Prevention%20of%20Lead%20Poisoning%20in%20Children&f=false
6b) Myers et al., Postnatal Exposure to Methyl Mercury from Fish Consumption: a Review and New Data from the Seychelles Child Development Study, Neurotoxicology. May 2009; 30(3): 338–349. Published online Jan 21, 2009. doi: 10.1016/j.neuro.2009.01.005 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743883 Also see footnote 5c above.
6c) U.S. ATSDR, Public Health Service, Toxicological Profile for Mercury, at http://www.atsdr.cdc.gov/toxprofiles/tp46.pdf, p. 137 Note that mercury has been reported by a recognized expert to “kill neurons as they are born;” (Rodier, “Developing Brain as a Target of Toxicity,” Environmental Health Perspectives, at www.ncbi.nlm.nih.gov/pmc/articles/PMC1518932/pdf/envhper00365-0077.pdf)
6e) Amin et al., Is Neonatal Jaundice Associated with Autism Spectrum Disorders: A Systematic Review, J Autism Dev Disord. Author manuscript; available in PMC 2015 Jan 6 PMCID: PMC4285414, NIHMSID: NIHMS647119 found at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4285414/
7) Re: Mercury levels in breast milk:
- U.S. ATSDR document on mercury at www.atsdr.cdc.gov/toxprofiles/tp46-c5.pdf, p. 443
- Code of Federal Regulations, Title 21, Chapter 1, Subchapter B, Part 165, Subpart B, Sec. 165-110 at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=165.110
7a) Pesticides in the Diets of Infants and Children, Commission on Life Sciences, National Research Council, National Academy Press, Washington, D.C. 1993, p. 60 at http://www.nap.edu/openbook.php?record_id=2126
7b) WHO: State of the Science of Endocrine Disrupting Chemicals - 2012, accessible at http://www.who.int/ceh/publications/endocrine/en/
9) Breastfeeding and Autism P. G. Williams, MD, Pediatrics, University of Louisville, and L. L. Sears, MD, presented at International Meeting for Autism Research, May 22, 2010, Philadelphia Marriot, found at https://imfar.confex.com/imfar/2010/webprogram/Paper6362.html) This study found that 35% of autism cases had been breastfed for a certain period, compared with 13% and 14% in the control group and in the same state.
- Dodds et al., The Role of Prenatal, Obstetric and Neonatal Factors in the Development of Autism, J Autism Dev Disord (2011) 41:891–902 DOI 10.1007/s10803-010-1114-8, Table 6, at http://autism.medicine.dal.ca/research/documents/2011DoddsetalJAutDevDisord.pdf This 2010 Canadian study, drawing data from a population-based “clinically-rich perinatal database,” investigated a very large population, nearly 130,000 births. Data from almost 127,000 of those children (those without identified genetic risk of autism) went into the study’s finding that there was a 25% increased risk of autism among children who were breastfed at discharge from the hospital.
- Whitely et al., Trends in Developmental, Behavioral and Somatic Factors by Diagnostic Sub-group in Pervasive Developmental Disorders: A Follow-up Analysis, pp. 10, 14 Autism Insights 2009:1 3-17 at http://www.la-press.com/redirect_file.php?fileId=2425&filename=1725-AUI-Trends-in-Developmental,-Behavioral-and-Somatic-Factors-by-Diagnostic-.pdf&fileType=pdf This study found that 65% of autism cases had been breastfed for a certain period; the authors looked at a comparison figure of 54%, but that figure was unrealistically high, since it came from a study (Pontin et al.) of breastfeeding by mothers largely from “more affluent families”, who breastfeed at unusually high rates in the U.K. For breastfeeding prevalence data that would apply to the general U.K. population, the authors of the Pontin study referred the reader to Infant Feeding 1995 (Foster et al.); examination of the data in that book reveals that a figure in the upper 20%’s would apply for the equivalent period (just after four weeks). That is also as was found in the U.K. Infant Feeding Survey - UK, 2010 Publication date: November 20, 2012, Chapter 2, at http://www.hscic.gov.uk/catalogue/PUB08694/ifs-uk-2010-chap2-inc-prev-dur.pdf
10) Durkin et al., Advanced Parental Age and the Risk of Autism Spectrum Disorder, Am J Epidemiol. 2008 December 1; 168(11) Table 3’s “Birth order” section, at www.ncbi.nlm.nih.gov/pmc/articles/PMC2638544; this study was referred to in 2009 as the largest of its kind (in “US researchers find link between age, birth order and autism,” theguardian.com, 7 January 2009); it studied a birth cohort of over 250,000. Durkin et al. also referred to another study supporting correlation of increased autism with earlier birth order: Glasson et al. Perinatal factors and the development of autism. Arch Gen Psychiatry. 2004;61(6):618–627.)
11) Ryan et al., Program for Women, Infants, and Children Participants, 1978 -2003: Lower Breastfeeding Rates Persist … in journal Pediatrics, at http://pediatrics.aappublications.org/content/117/4/1136.full.pdf+html , Table 2, “Parity” section.
13) -- PCDDs, PCDFs, and PCBs concentrations in breast milk from two areas in Korea: body burden of mothers and implications for feeding infants, Jiyeon Yang et al. Chemosphere 46 (2002) 419–428);
also see Ennaceur et al. study that is source of chart shown.
13a) Infant Exposure to Chemicals in Breast Milk in the United States: What We Need to Learn From a Breast Milk Monitoring Program, LaKind, et al., Children's Health Review Environmental Health Perspectives • Vol. 109 | No. 1 | January 2001. p. 81, at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1242055/pdf/ehp0109-000075.pdf
14) Jones et al., Attention to eyes is present but in decline in 2-6-month-old infants later diagnosed with autism: Nature:(2013) DOI:doi:10.1038/nature at www.pediatrics.emory.edu/documents/divisions/autism/Jones_Klin_2013.pdf
15) Rossignol et al., Environmental toxicants and autism spectrum disorders: a systematic reviewTransl Psychiatry. Feb 2014; 4(2): e360. Published online Feb 11, 2014. PMCID: PMC3944636 at www.ncbi.nlm.nih.gov/pmc/articles/PMC3944636
16) Exploration of Perinatal Pharmacokinetic Issues Contract No. 68-C-99-238, Task Order No. 13 Prepared for EPA by: Versar, Inc. EPA/630/R-01/004, Section 126.96.36.199, at www.epa.gov/raf/publications/pdfs/PPKFINAL.PDF
17) Surgeon General's Call to Action to Support Breastfeeding, 2011, Figure 1 and p. 33 at www.surgeongeneral.gov/library/calls/breastfeeding/calltoactiontosupportbreastfeeding.pdf
18) Sec. II.B of Brominated Flame Retardants, Third annual report to the Maine Legislature, 2007, D Rice et al. http://www.maine.gov/dep/waste/publications/legislativereports/documents/finalrptjan07.pdf, citing Li et al., 2005a Also Table 3 of Developmental Neurotoxicity of Polybrominated Diphenyl Ether (PBDE) Flame Retardants, Costa et al., Neurotoxicology. 2007 November; 28(6): NIHMS34875 at www.ncbi.nlm.nih.gov/pmc/articles/PMC2118052
19) Philippe Grandjean, in “Neurodevelopmental Disorders” in Children’s Health and Environment: A Review of Evidence, published by WHO, Regional Office for Europe, at www.euro.who.int/__data/assets/pdf_file/0007/98251/E75518.pdf p. 67 Also, P. Grandjean, Methylmercury Exposure Biomarkers as Indicators of Neurotoxicity in Children Aged 7 Years, American Journal of Epidemiology 1999, The Johns Hopkins University School of Hygiene and Public Health at http://aje.oxfordjournals.org/content/150/3/301.full.pdf : “The nervous system is particularly vulnerable to effects from neurotoxicants such as methylmercury during the last two trimesters of pregnancy and during early postnatal life.”
20) Rodier, “Developing Brain as a Target of Toxicity,” Environmental Health Perspectives, at www.ncbi.nlm.nih.gov/pmc/articles/PMC1518932/pdf/envhper00365-0077.pdf Also see Rice et al., Critical Periods of Vulnerability for the Developing Nervous System: Evidence from Humans and Animal Models, EPA National Center for Environmental Assessment, at www.ncbi.nlm.nih.gov/pmc/articles/PMC1637807, p. 515.
20a) ATSDR publication at http://www.atsdr.cdc.gov/sites/toxzine/mercury_toxzine.html
21a) Section 6.4.2 of Mercury Study Report to Congress c7o032-1-1, Office of Air Quality Planning & Standards and Office of Research and Development Volume VII at http://www.epa.gov/ttn/oarpg/t3/reports/volume7.pdf
21c) Pesticides in the Diets of Infants and Children, Commission on Life Sciences, National Research Council, National Academy Press, Washington, D.C. 1993, p. 25 at http://www.nap.edu/openbook.php?record_id=2126&page=43
21d) U.S. ATSDR, Public Health Service, Toxicological Profile for Mercury at www.atsdr.cdc.gov/toxprofiles/tp46.pdf, p. 214 re “deranged” neuronal migration. Also Section 1.6 re particularly sensitive periods of neurological development.
21e) EPA-452/R-97-009 December 1997 p. 5-29 (Section 5.6.1) at http://www.epa.gov/ttn/oarpg/t3/reports/volume7.pdf
22) P. Grandjean et al., Attenuated growth of breast-fed children exposed to increased concentrations of methylmercury and polychlorinated biphenyls, FASEB J. (February 5, 2003) 10.1096/fj.02– 0661fje at www.fasebj.org/content/17/6/699.full.pdf
23) Burbacher et al., Comparison of Blood and Brain Mercury Levels in Infant Monkeys Exposed to Methylmercury or Vaccines Containing Thimerosal, (Oral Mg Kinetics section) Environ Health Perspect. 2005 August; 113(8): 1015–1021, PMCID: PMC1280342 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1280342
24) Judy L. Cameron in Chapter 5, "Effects of Sex Hormones on Brain Development," in Handbook of Developmental Cognitive Neuroscience, MIT Press. Selected pages can be found at no charge at www.worldcat.org/title/handbook-of-developmental-cognitive-neuroscience/oclc/45059115/viewport or at that organization’s website, doing a search including the above book title and “sex steroids.”
25) ”Steroid Hormones and Brain Development: Some Guidelines for Understanding Actions of Pseudohormones and Other Toxic Agents" by Bruce S. McEwen, Laboratory of Neuroendocrinology, Rockefeller University, New York, NY (published in Environmental Health Perspectives Vol. 74, pp. 177-184, 1987 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1474508/pdf/envhper00433-0170.pdf). Research in the author's laboratory was supported by NIH Grant NS07080 and NIMH Grant MH41256.
26) Infant Exposure to Dioxin-like Compounds in Breast Milk Lorber (Senior Scientist at EPA) and Phillips Vol. 110., No. 6 June 2002 • Environmental Health Perspectives at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240886/pdf/ehp0110-a00325.pdf, 242 pg at initiation; this should be compared with data from following: U.K. Food Standards Agency Food Survey Information Sheet 49/04 Mar. 2004, Dioxins and Dioxin-Like PCBs in Infant Formulae, found at www.food.gov.uk/multimedia/pdfs/fsis4904dioxinsinfantformula.pdf
Compatible figures were found in Weijs PJ, et al., Dioxin and dioxin-like PCB exposure of non-breastfed Dutch infants, Chemosphere 2006 Aug;64(9):1521-5. Epub 2006 Jan 25 at www.ncbi.nlm.nih.gov/pubmed/16442144
27) Mann et al., Commentary, The neonatal period: a critical interval in male primate development Journal of Endocrinology (1996) 149, 191–197 http://joe.endocrinology-journals.org/content/149/2/191.full.pdf+html); also (Sex, Hormones and Behaviour p. 321 - CIBA Foundation Symp.2009 - Wiley, Pub. At http://books.google.com/books)
27a) In a 2014 study, the authors stated that a recent meta-analysis of 25 studies reported data “supporting the theory of specific underconnectivity in autism focused on tracts supporting auditory information and language processing.” Using DTI (diffusion tensor imaging), the authors found that both SPD (Sensory Processing Disorder) and ASD cohorts demonstrated decreased connectivity in brain tracts involved in sensory perception and multisensory integration. And they found that “the ASD group alone shows impaired connectivity, relative to controls, in temporal tracts thought to subserve social-emotional processing.” (Chang et al., Autism and Sensory Processing Disorders: Shared White Matter Disruption in Sensory Pathways but Divergent Connectivity in Social-Emotional Pathways, Plos One, July 2014, at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0103038)
27b) A 2009 study noted, based on many studies, that “Neurodevelopmental disorders are associated with altered patterns of neuronal connectivity.” (Yang et al., Developmental Exposure to Polychlorinated Biphenyls Interferes with Experience-Dependent Dendritic Plasticity and Ryanodine Receptor Expression in Weanling Rats, Environ Health Perspect;, March 2009, DOI:10.1289/ehp.11771 at http://ehp.niehs.nih.gov/11771)
27c) Stamou et al., Neuronal connectivity as a convergent target of gene-environment interactions that confer risk for Autism Spectrum Disorders, Neurotoxicology and teratology 2013 Mar-Apr, at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3610799/.
27d) PLoS One. 2014 Aug 20;9(8):e105176. doi: 10.1371/journal.pone.0105176. eCollection 2014. at http://www.ncbi.nlm.nih.gov/pubmed/25140874Functional connectivity in the first year of life in infants at risk for autism spectrum disorder: an EEG study,
Keehn et al.,Functional connectivity in the first year of life in infants at-risk for autism: a preliminary near-infrared spectroscopy study Front Hum Neurosci. 2013 Aug 6;7:444. doi: 10.3389/fnhum.2013.00444. eCollection 2013. at http://www.ncbi.nlm.nih.gov/pubmed/23964223
Kana et al., Brain connectivity in autism, Frontiers in Human Neuroscience, 2014, at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041005/
Tang et al., Loss of mTOR-Dependent Macroautophagy Causes Autistic-like Synaptic Pruning Deficits at http://www.cell.com/neuron/abstract/S0896-6273%2814%2900651-5
28) Life Sciences Learning Center, University of Rochester, 2013, Brain Development and Toxins, p. 3, at http://www.urmc.rochester.edu/MediaLibraries/URMCMedia/life-sciences-learning-center/documents/2013-14Neuroscience/Brain-Development-and-Toxins-TEACHER-9-17-13.pdf
28c) A publication of the Executive Director of the Center for Sensorimotor Neural Engineering at the University of Washington refers to a five-fold increase in formation of synapses postnatally compared with prenatally. (Chudler, Brain Plasticity -- What is It? at https://faculty.washington.edu/chudler/plast.html, citing Gopnic, A., Meltzoff, A., Kuhl, P. (1999). The Scientist in the Crib: What Early Learning Tells Us About the Mind, New York, NY: HarperCollins Publishers)
It appears to be very widely accepted that “During the first three years of life in humans, there is a period of rapid synapse formation that connects nerve cells into functioning circuits. This time of rapid synapse formation is the critical period in brain development.”(28d) (Emphasis on “the” is in the original.) The New York Times writer just quoted (who for eighteen years had been following research and awarding grants in education, cognitive psychology, and neuroscience at three foundations) points out a lack of scientific evidence as to what specific kind of external stimulation is optimal during that period, but he apparently sees no disagreement about the existence of the birth-to-age-three “early stage of exuberant synapse formation.” (John T. Bruer, “The Myth of the First Three Years: A New Understanding of Early Brain Development and Lifelong Learning,” in NY Times Books section at https://www.nytimes.com/books/first/b/bruer-myth.html)
See also Tau et al., Normal Development of Brain Circuits, Neuropsychopharmacology. Jan 2010; 35(1): 147–168. Published online Sep 30, 2009. doi: 10.1038/npp.2009.115 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3055433/
28e) “UC Davis MIND Institute study finds association between maternal exposure to agricultural pesticides, autism in offspring”, in News from UC Davis Health System, June 22, 2014, at http://www.ucdmc.ucdavis.edu/publish/news/newsroom/8978
28f) Grandjean P, Landrigan PJ. Developmental neurotoxicity of industrial chemicals. Lancet. 2006;368:2167–2178. at http://www.reach-compliance.eu/english/documents/studies/neurotoxity/PGrandjean-PjLandrigan.pdf p. 2
28g) Jensen, A.A. et al, Chemical Contaminants in Human Milk, CRC Press, Inc., Boca Raton, Ann Arbor, Boston, 1991, p 15. Findings of above confirmed in animal tests, with even greater contrasts, in Ahlborg et al., Risk Assessment of Polychlorinated Biphenyls (PCBs), Nordic Council of Ministers, Copenhagen. Report NORD 1992; 26
28h) International Programme On Chemical Safety, Environmental Health Criteria 101: Methylmercury (a publication of WHO, Geneva, 1990) at http://www.inchem.org/documents/ehc/ehc/ehc101.htm#subsectionnumber:9.1.2
29) Re: EPA’s RfD for dioxin: At www.epa.gov/iris/supdocs/dioxinv1sup.pdf in section 4.3.5, at end of that section, "...the resulting RfD in standard units is 7 × 10−10 mg/kg-day." (that is, O.7 pg of TEQ/kg-d)
Re: breastfed infants’ exposures to dioxins, in U.S. and internationally:
- Lorber et al., Infant Exposure to Dioxin-like Compounds in Breast Milk, Vol. 110 No. 6, June 2002, Environmental Health Perspectives at http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=54708#Download, indicating 242 pg of TEQ/kg-d at initiation of breastfeeding.
- Focant et al., Levels of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and polychlorinated biphenyls in human milk from different regions of France, Science of The Total Environment, Volumes 452–453, 1 May 2013, Pages 155–162 abstract at http://www.sciencedirect.com/science/article/pii/S0048969713002404
- Yang J, et al., PCDDs, PCDFs, and PCBs concentrations in breast milk from two areas in Korea: body burden of mothers and implications for feeding infants. Chemosphere. 2002 Jan;46(3):419-28. At www.ncbi.nlm.nih.gov/pubmed/11829398
- Bencko V et al., Exposure of breast-fed children in the Czech Republic to PCDDs, PCDFs, and dioxin-like PCBs. Environ Toxicol Pharmacol. 2004 Nov;18(2):83-90. Abstract at http://www.ncbi.nlm.nih.gov/pubmed/21782737/
- Nakatani T, et al., Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and coplanar polychlorinated biphenyls in human milk in Osaka City, Japan Arch Environ Contam Toxicol. 2005 Jul;49(1):131-40. Epub 2005 Jun 22. Found at http://www.ncbi.nlm.nih.gov/pubmed/15983863
- Deng B, et al., Levels and profiles of PCDD/Fs, PCBs in mothers' milk in Shenzhen of China: estimation of breast-fed infants' intakes.Environ Int. 2012 Jul;42:47-52.. At www.ncbi.nlm.nih.gov/pubmed/21531025
- Chovancová J, et al., PCDD, PCDF, PCB and PBDE concentrations in breast milk of mothers residing in selected areas of Slovakia Chemosphere. 2011 May;83(10):1383-90. doi: 10.1016/j. At www.ncbi.nlm.nih.gov/pubmed/21474162
- J Grigg, Environmental toxins; their impact on children’s health, Arch Dis Child 2004;89:244-250 doi:10.1136/adc.2002.022202 at http://adc.bmj.com/content/89/3/244.full
30) Re: PBDEs ingested by breastfed infants:
-Table 5-4 of EPA (2010) An exposure assessment of polybrominated diphenyl ethers. National Center for Environmental Assessment, Washington, DC; EPA/600/R-08/086F. http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=210404, Schechter study in first page of table, showing 306 ng/kg-d as exposure for breastfed infants.
- Costa et al.,Developmental Neurotoxicity Of Polybrominated Diphenyl Ether (PBDE) Flame Retardants, Neurotoxicology. 2007 November; 28(6): 1047–1067. at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118052 Last paragraph of “Relevance to Humans” section, re up to 4.1 micrograms (4100 ng)/kg-day exposure of infants
Regarding prevalence of tetraBDEs, see Costa LG, et al., Polybrominated diphenyl ether (PBDE) flame retardants: environmental contamination, human body burden and potential adverse health effects. Acta Biomed. 2008 Dec;79(3):172-83 at www.ncbi.nlm.nih.gov/pubmed/19260376.
-- RFD for PBDEs: EPA Technical Fact Sheet on Polybrominitated Diphenyl Eithers (PBDEs) and PBBs, p. 4 re RfD of 1 x 10-4 mg/kg/day (100 ng/kg-d) for BDE-47 and BDE 99 at www2.epa.gov/sites/production/files/2014-03/documents/ffrrofactsheet_contaminant_perchlorate_january2014_final_0.pdf
30a) Mercury typically 8 parts per billion in breast milk, according to U.S. ATSDR document on mercury at http://www.atsdr.cdc.gov/toxprofiles/tp46-c5.pdf, p. 443, which compares with1 microgram per liter (1 microgram per billion micrograms), or 1 part per billion, the WHO guideline value for drinking water: (WHO, Mercury in Drinking-water Background document for development of WHO Guidelines for Drinking-water Quality WHO/SDE/WSH/03.04/10 at http://www.who.int/water_sanitation_health/dwq/chemicals/en/mercury.pdf p. 8 Accessed 4/8/2014)
31) P. Grandjean et al., Human Milk as a Source of Methylmercury Exposure in Infants, Environmental Health Perspectives, accepted Oct. 1993 www.ncbi.nlm.nih.gov/pmc/articles/PMC1567218/pdf with compatible results found in other studies: Marques RC, et al., Hair mercury in breast-fed infants exposed to thimerosal-preserved vaccines. Eur J Pediatr. 2007 Sep;166(9):935-41 at www.sarnet.org/lib/VaxHgBrazil1.pdf; the authors found that, during 6 months of breastfeeding, infants' hair-Hg increased 446%, 40% of which was from vaccinations. Also Exploration Of Perinatal Pharmacokinetic Issues Contract No. 68-C-99-238, Task Order No. 13 Prepared for: Office of Research and Development, U.S. Environmental Protection Agency Prepared by: Versar, Inc. EPA/630/R-01/004 Section 188.8.131.52, at www.epa.gov/raf/publications/pdfs/PPKFINAL.PDF
31a) U.S. Agency for Toxic Substances and Disease Registry, Toxicological Profile for Polychlorinated Biphenyls (PCBs), 2000, at http://www.atsdr.cdc.gov/toxprofiles/tp17.pdf This ATSDR report quotes a range of concentrations of PCBs in human milk as from 238 to 271 ng/g lipid weight. 1 g lipid weight = about 25g whole weight (assuming 4% fat in human milk). So the concentrations found in the studies were about 250 ng/25g whole weight, which = 10ng/g whole weight. 1 g (gram) = 1 ml of water., so the 10 ng/g whole weight is the same as 10ng/ml. That is the same as 10,000 ng per liter, which is the same as .01 mg/liter. So the levels of PCBs in human milk seem to be about .01 mg/liter, compared with .0005 mg/liter, the maximum allowed by law in U.S. public water systems. That is, about 20 times the concentration that would be allowed in public water systems. (U.S.EPA, Drinking Water Contaminants, National Primary Drinking Water Regulations, at http://water.epa.gov/drink/contaminants/index.cfm#Organic)
31b) re PBDEs: EPA: Emerging Contaminants: Polybrominated Diphenyl Ethers (PBDE) and Polybrominated Biphenyls (PBB) , 2008, at http://nepis.epa.gov/Adobe/PDF/P1000L3S.PDF.
Also: EPA, Building a Database of Developmental Neurotoxicants: Evidence from Human and Animal Studies at http://epa.gov/ncct/toxcast/files/summit/48P%20Mundy%20TDAS.pdf
Dioxins, mercury and PCBs have long been known to be neurodevelopmental toxins.
32) Re: dioxins in formula less than 1% of dioxins in breast milk:
- Re dioxins in breast milk, see footnote 26 above.
- Re dioxins in formula: U.K. Food Standards Agency Food Survey Information Sheet 49/04 MARCH 2004, Dioxins and Dioxin-Like PCBs in Infant Formulae, found at http://www.food.gov.uk/multimedia/pdfs/fsis4904dioxinsinfantformula.pdf
- Compatible figures were found in Weijs PJ, et al., Dioxin and dioxin-like PCB exposure of non-breastfed Dutch infants. Chemosphere. 2006 Aug;64(9):1521-5. Epub 2006 Jan 25 at www.ncbi.nlm.nih.gov/pubmed/16442144
Re: PBDEs in formula about 3% of concentration in breast milk:
- Re PBDEs in breast milk, 1,056 pg/g wet weight: Schecter et al., Polybrominated Diphenyl Ether (PBDE) Levels in an Expanded Market Basket Survey of U.S. Food and Estimated PBDE Dietary Intake by Age and Sex, Environ Health Perspect. Oct 2006; 114(10): 1515–1520, 4th paragraph from end, at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1626425 This study was cited in the EPA document below, Section 5.6.2, 2nd paragraph.
- In formula: Section 4.7 , p. 4-77, 2nd paragraph (citing Schechter et al., finding of 25 and 32 pg/g wwt, ) of U.S. EPA (2010) An exposure assessment of polybrominated diphenyl ethers. http:/cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=210404
Re: Mercury in formula less than 1% as high as in human milk:
Mercury levels in breast milk:
- U.S. ATSDR document on mercury at www.atsdr.cdc.gov/toxprofiles/tp46-c5.pdf, p. 443
Mercury in infant formula:
- Food Additives & Contaminants: Part B: Surveillance Volume 5, Issue 1, 2012 Robert W. Dabeka et al., Survey of total mercury in infant formulae and oral electrolytes sold in Canada DOI: 10.1080/19393210.2012.658087 at
Re: PCBs in infant formula typically less than 1% but up to about 4% as high as in human milk:
- In breast milk: About 250 ng/g lipid weight. In soy-based formula: about 10 ng/g lipid weight. U.S. Agency for Toxic Substances and Disease Registry, Toxicological Profile for Polychlorinated Biphenyls (PCBs), 2000, pp. 560, 573, at http://www.atsdr.cdc.gov/toxprofiles/tp17.pdf Data does not appear to be available for PCBs in cow’s-milk-based infant formula, but data for whole milk could give an approximation, as follows: adding together the figures for the two kinds of PCBs in this study provides a range of 52 to 2455 ng/kg fat, which equals .05 to 2.45 ng/g fat (lipid) (Krokos et al., Levels of selected ortho and non-ortho polychlorinated biphenyls in UK retail milk, Chemosphere. 1996 Feb;32(4):667-73. at www.ncbi.nlm.nih.gov/pubmed/8867147)
32a) The author of this article wrote letters to the seven scientists who comprise the science team at the major autism-advocacy organization, Autism Speaks, asking if they are aware of any avenue other than breastfeeding by which developing brains are widely exposed to neurodevelopmental toxins at levels exceeding established safe levels. As of six months later, no reply that was received suggested any other such avenue.
33) Quinn et al.,Investigating Intergenerational Differences in Human PCB Exposure due to Variable Emissions and Reproductive Behaviors, Environ Health Perspect. May 2011; 119(5): 641–646. at www.ncbi.nlm.nih.gov/pmc/articles/PMC3094414
33a) Measured Prenatal and Estimated Postnatal Levels of Polychlorinated Biphenyls (PCBs) and ADHD-Related Behaviors in 8-Year-Old Children, Figure 2, Environ Health Perspect; DOI:10.1289/ehp.1408084 , Vol. 123, Issue 9, Sept. 2015, at http://ehp.niehs.nih.gov/1408084
34) Intake, fecal excretion, and body burden of polychlorinated dibenzo-p-dioxins and dibenzofurans in breast-fed and formula-fed infants. Abraham K, Knoll A, Ende M, Päpke O, Helge H. Children's Hospital, Virchow-Klinikum, Humboldt-Universität Berlin, Germany. at www.ncbi.nlm.nih.gov/pubmed/8910931 This study was cited in a 2002 EPA document ("Infant Exposure to Dioxin-like Compounds in Breast Milk") that apparently considered it to be fully valid.
35) Infant Exposure to Dioxin-like Compounds in Breast Milk, Lorber and Phillips Volume 110 | Number 6 | June 2002 • Environmental Health Perspectives www.ncbi.nlm.nih.gov/pmc/articles/PMC1240886/pdf/ehp0110-a00325.pdf Also EPA Home/Research/Environmental Assessment: An Evaluation of Infant Exposure to Dioxin-Like Compounds in Breast Milk, Matthew Lorber (National Center for Environmental Assessment, Office of Research and
36) CDC’s MMWR National Surveillance for Asthma -- United States, 1980-2004, Table 29, at www.cdc.gov/mmwr/preview/mmwrhtml/ss5608a1.htm Re allergies: CDC’s Health United States 2011, Table 46, p. 3, at www.cdc.gov/nchs/data/hus/contents2011.htm1046 Type 2 Diabetes in Children and Young Adults: A “New Epidemic,” Francine Ratner Kaufman, MD Clinical Diabetes • Volume 20, Number 4, 2002 at http://clinical.diabetesjournals.org/content/20/4/217.full.pdf+html Re ADHD: see www.breastfeeding-and-ADHD.info for substantial evidence about the time trend of ADHD in the U.S.
37) There appears to be no data recording measurements of the same classification of mental retardation continuously in recent decades. However, there is substantial data concerning mental difficulties among children through the decades. This shows a disproportionate and increasing number of male children with disabilities, especially mental impairment, with the gender ratio becoming more uneven among more recent births. This is evident in a National Academies Press publication (TABLE 3-1 of The Future of Disability in America, Institute of Medicine (US) Committee on Disability in America; Field MJ, Jette AM, editors, National Academies Press (US), 2007, found at www.ncbi.nlm.nih.gov/books/NBK11437/table/a2001315cttt00007/?report=objectonly . The U.S. Census Bureau’s question that was apparently used for obtaining this data asks, "Because of a physical, mental or emotional condition, does this person have serious difficulty concentrating, remembering, or making decisions?” The percentage of males said to have such mental difficulties who were born since the early 1990’s is twice as high as the percentage of females in the same age group (that is, 5.2% for male children nationwide, which includes many of those with autism, vs. 2.6% of females); this is in sharp contrast with the apparently gender-equal numbers that apply to those born in the half-century leading up to the mid-1970’s. And those born in the period between the mid-1970’s and the early 1990’s had an intermediate male-female disproportion of impairments. This data is from U.S. Census Bureau Table B18104: SEX BY AGE BY COGNITIVE DISABILITY Universe: Civilian non-institutionalized population 5 years and over. Data Set: 2008-2010 American Community Survey 3-Year Estimates (accessed Jan. 2012 at http://factfinder2.census.gov , using their search process)
38) Re mental retardation trend: National Center for Health Statistics, Healthy People 2000 Review, 1997. Public Health Service. Lib. of Congress Cat. No. 76-641496, Figure R, found at www.cdc.gov/nchs/data/hp2000/2k97.pdf Also see www.retardation.info .
40) See Section 1.c of www.breastfeeding-vs-formula.info, which includes citations of dozens of peer-reviewed or other authoritative sources.
40a) Verner et al., Alteration of infant attention and activity by polychlorinated biphenyls: unravelling critical windows of susceptibility using physiologically based pharmacokinetic modeling, Neurtoxicology, 2010;31(5):424-31
41) Winneke G. et al., Developmental aspects of environmental neurotoxicology: lessons from lead and polychlorinated biphenyls. J Neurol Sci. 2011 Sep 15;308(1-2):9-15. doi: 10.1016/j.jns.2011.05.020. Epub 2011 Jun 15. at www.ncbi.nlm.nih.gov/pubmed/21679971
41b) Verner et al., Measured Prenatal and Estimated Postnatal Levels of Polychlorinated Biphenyls (PCBs) and ADHD-Related Behaviors in 8-Year-Old Children, Environmental Health Perspectives, 2015, http://dx.doi.org/10.1289/ehp.1408084, at http://ehp.niehs.nih.gov/wp-content/uploads/advpub/2015/3/ehp.1408084.acco.pdf
41c) -- Vreugdenhil et al., Effects of Perinatal Exposure to PCBs on Neuropsychological Functions in the Rotterdam Cohort at 9 Years of Age, Neuropsychology, 2004, Vol. 18, No. 1, 185–193 at http://psycnet.apa.org/journals/neu/18/1/185.pdf
41d) Schantz et al., Impairments of memory and learning in older adults exposed to polychlorinated biphenyls via consumption of Great Lakes fish, Environ Health Perspect, 2001 Jun;109(6):605-11.at http://www.ncbi.nlm.nih.gov/pubmed/11445515
42) Chao et al., Levels of Breast Milk PBDEs From Southern Taiwan and Their Potential Impact on Neurodevelopment, Pediatric Research (2011) 70, 596–600; doi:10.1203/PDR.0b013e3182320b9b at www.nature.com/pr/journal/v70/n6/full/pr20111086a.html
43) Porterfield, Vulnerability of the Developing Brain to Thyroid Abnormalities: Environmental Insults to the Thyroid System, in Environ Health Perspect 102(Suppl 2):125-130 (1994) at www.ncbi.nlm.nih.gov/pmc/articles/PMC1567088/pdf/envhper00398-0125.pdf
43a) Schell et al., Relationships of Polychlorinated Biphenyls and Dichlorodiphenyldichloroethylene (p,p’-DDE) with Testosterone Levels in Adolescent Males, Environ Health Perspect; DOI:10.1289/ehp.1205984 at http://ehp.niehs.nih.gov/1205984
43b) Jusko et al., Prenatal and Postnatal Serum PCB Concentrations and Cochlear Function in Children at 45 Months of Age, Environmental Health Perspectives, 22 July 2014 (Advance Pub.) at http://ehp.niehs.nih.gov/wp-content/uploads/advpub/2014/7/ehp.1307473.pdf
44) Nagayama et al., Postnatal exposure to chlorinated dioxins and related chemicals on thyroid hormone status in Japanese breast-fed infants, Chemosphere. 1998 Oct-Nov;37(9-12):1789-93.at www.ncbi.nlm.nih.gov/pubmed/9828307
45) Schantz et al., Effects of PCB Exposure on Neuropsychological Function in Children Environmental Health Perspectives, Vol. 111 at at www.ncbi.nlm.nih.gov/pmc/articles/PMC1241394/pdf/ehp0111-000357.pdf p. 363
46) Agency for Healthcare Research and Quality, U.S. DHHS, Systems to Rate the Strength of Scientific Evidence, Evidence Report/Technology Assessment: Number 47 http://archive.ahrq.gov/clinic/epcsums/strengthsum.pdf
47) Zoeller et al., Thyroid Hormone, Brain Development, and the Environment, Environmental Health Perspectives • VOLUME 110 | SUPPLEMENT 3 | JUNE 2002 at www.bio.umass.edu/biology/zoeller/pdf/zlabEHP.pdf
47a) Lee et al., Association of serum concentrations of persistent organic pollutants with the prevalence of learning disability and attention deficit disorder, J Epidemiol Community Health 2007;61:591–596. doi: 10.1136/jech.2006.054700 at http://jech.bmj.com/content/61/7/591.full.pdf+html.
47b) Lorber et al., Infant Exposure to Dioxin-like Compounds in Breast Milk, Volume 110 | Number 6 | June 2002 • Environmental Health Perspectives (a peer-reviewed journal published by the National Institute of Environmental Health Sciences of NIH) http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=54708#Download
47d) Center on the Developing Child at Harvard University, National Scientific Council on the Developing Child: Early Exposure to Toxic Substances Damages Brain Architecture, 2006; link for this publication at http://developingchild.harvard.edu/index.php/resources/reports_and_working_papers/working_papers/wp4/
47e) Landrigan et al., Pesticides and Inner-City Children: Exposures, Risks, and Prevention, Environmental Health Perspectives * Vol 107, Supplement 3 * June 1999, at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1566233/pdf/envhper00520-0047.pdf
48) See Section 2, cont.; also a 2006 Taiwanese study found that, of the three sources of infant mercury exposure, inhalation, dermal exposure, and ingestion (breast milk), 96 to 99.6% of the total exposure was from breastfeeding.(Chien LC, et al., Analysis of the health risk of exposure to breast milk mercury in infants in Taiwan.Chemosphere. 2006 Jun;64(1):79-85. Epub 2006 Jan 25 at www.ncbi.nlm.nih.gov/pubmed/16442149 Also a German study found that, at 11 months of age, the dioxin toxicity-equivalent concentrations in formula-fed infants were about 10 times lower than in the infants that were breast-fed for six to seven months. (Intake, fecal excretion, and body burden of polychlorinated dibenzo-p-dioxins and dibenzofurans in breast-fed and formula-fed infants. Abraham et al., Children's Hospital, Virchow-Klinikum, Humboldt-Universität Berlin. at www.ncbi.nlm.nih.gov/pubmed/8910931 This study was cited in a 2002 EPA document ("Infant Exposure to Dioxin-like Compounds in Breast Milk"))
49) Banaschewski et al., Autism and ADHD across the life span. Differential diagnoses or comorbidity? Nervenarzt. 2011 May;82(5):573-80. doi: 10.1007/s00115-010-3239-6. [Article in German] at www.ncbi.nlm.nih.gov/pubmed/21484168
50) "ADHD Can Cause Lifelong Problems, Study Finds." In HealthDay News of NIH, in Medline Plus Weekly Digest Bulletin of 12/23/12 at www.nlm.nih.gov/medlineplus/news/fullstory_132091.html
51) See Sections 2.a and 2.c of www.breastfeeding-studies.info
52) Cohly et al., Immunological findings in autism, Int Rev Neurobiol. 2005;71:317-41. at http://www.ncbi.nlm.nih.gov/pubmed/16512356
52a) Adams et al., Workshop to Identify Critical Windows of Exposure for Children's Health:Neurobehavioral Work Group Summary, Environmental Health Perspectives * Vol 108, Supplement 3 * June 2000
52b) Danish Health and Medicines Authority, 2013, Health risks of PCB in the indoor climate in Denmark, at http://sundhedsstyrelsen.dk/publ/Publ2013/12dec/HAofPCBindoorDK_en.pdf, pp.76-78, 95
52c) Danish Health and Medicines Authority, 2013, Health risks of PCB in the indoor climate in Denmark, at http://sundhedsstyrelsen.dk/publ/Publ2013/12dec/HAofPCBindoorDK_en.pdf, p.91
53) Seelbach et al., Polychlorinated Biphenyls Disrupt Blood–Brain Barrier Integrity and Promote Brain Metastasis Formation, Environ Health Perspect. Apr 2010; 118(4): 479–484. Published online Oct 28, 2009. doi: 10.1289/ehp.0901334 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854723/
Also Selvakumar et al., Polychlorinated biphenyls impair blood-brain barrier integrity via disruption of tight junction proteins in cerebrum, cerebellum and hippocampus of female Wistar rats: neuropotential role of quercetin, Hum Exp Toxicol. 2013 Jul;32(7):706-20. doi: 10.1177/0960327112464798. Epub 2012 Nov 15. at http://www.ncbi.nlm.nih.gov/pubmed/23155198
54) See, as illustrations, the breastfeeding page to be found at www.womenshealth.gov or the breastfeeding position paper of the American Academy of Pediatrics to be found at www.aap.org, neither of which makes any mention of the known toxins contained in human milk, while they are making many assertions of presumed health benefits of breastfeeding based only on associations found in observational studies. (Those studies were recognized as being of the observational type by the Surgeon General, in the Surgeon General's Call to Action to Support Breastfeeding, 2011, at www.surgeongeneral.gov/library/calls/breastfeeding/calltoactiontosupportbreastfeeding.pdf, p. 33; observational studies are recognized by the U.S. Agency for Healthcare Research and Quality to be subject to false conclusions, at http://archive.ahrq.gov/clinic/epcsums/strengthsum.pdf)
55b) “More than 350 pollutants found in breast milk,” Geoffrey Lean, Environment Correspondent Sunday 11 July 1999 at http://www.independent.co.uk/news/more-than-350-pollutants-found-in-breast-milk-1105582.html See also U.K. government document on this subject, at http://cot.food.gov.uk/pdfs/cotsuremilk.pdf and
55c) American Men and Women of Science: A Biographical Directory of Today’s Leaders in Physical, Biological and Related Sciences. Detroit: Gale, 2008 Biography in Context. Web. 10 Mar. 2014 Gale Document Number: GALE|K3099111341 See also Standing up to the Lead Industry: An Interview with Herbert Needleman Author(s): David Rosner and Gerald MarkowitzSource: Public Health Reports (1974-), Vol. 120, No. 3 (May - Jun., 2005), pp. 330-337 Published by: Association of Schools of Public Health
56) Vandenberg et al., Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses, (Endocrine Reviews 33: 0000–0000, 2012) at http://insideclimatenews.org/sites/default/files/assets/2012-03/Endocrine%20Reviews%20article.pdf
57) Jens Walkowiak et al., Environmental exposure to polychlorinated biphenyls and quality of the home environment: effects on psychodevelopment in early childhood. Lancet 2001: 358: 1602-07 Abstract at www.thelancet.com/journals/lancet/article/PIIS0140-6736(01)06654-5/abstract
Bernard Weiss, Silent Latency Periods in Methylmercury Poisoning and in Neurodegenerative Disease, Environmental Health Perspectives • Volume 110 | Supplement 5 | October 2002 at www.ncbi.nlm.nih.gov/pmc/articles/PMC1241259/pdf/ehp110s-000851.pdf
Very much the same message is presented in Giordano et al., Review Article, Developmental Neurotoxicity: Some Old and New Issues, International Scholarly Research Network, ISRN Toxicology Volume 2012, Article ID 814795, doi:10.5402/2012/814795 at www.hindawi.com/isrn/toxicology/2012/814795/ref/
Rice et al., Critical Periods of Vulnerability for the Developing Nervous System: Evidence from Humans and Animal Models, p. 525 at www.ncbi.nlm.nih.gov/pmc/articles/PMC1637807/pdf/envhper00312-0143.pdf
57a) Gray: Comments on “Developmental neurotoxicity of PCBs in humans: What do we know and where
do we go from here?” at http://www.sciencedirect.com/science/article/pii/S0892036296900112
57b) p. 132 of U.S. ATSDR, Public Health Service, Toxicological Profile for Mercury at http://www.atsdr.cdc.gov/toxprofiles/tp46.pdf
57c) Boucher at al., Prenatal Exposure to Polychlorinated Biphenyls: A Neuropsychologic Analysis,
Environ Health Perspect. Jan 2009; 117(1): 7–16. PMCID: PMC2627868 at www.ncbi.nlm.nih.gov/pmc/articles/PMC2627868
57e) Statement by Dr. D.C. Rice before U.S. Senate Committee on Environment & Public Works, 07/29/2003 at http://www.epw.senate.gov/hearing_statements.cfm?id=212850
57f) Report on the Situation of Infant and Young Child Feeding in Seychelles, August 2011, IBFAN, The Committee on the Rights of the Child www.ibfan.org/art/IBFAN_CRC58%20-2011_Seychelles.pdf The data from the Seychelles (1.5% exclusive breastfeeding at 6 months in 2008) should be compared with the11.9% exclusive breastfeeding at 6 months in U.S. in 2008 (itself having some of the lowest breastfeeding rates in the world), according to CDC data at www.cdc.gov/breastfeeding/pdf/2008BreastfeedingReportCard.pdf, top of 2nd page. This is from what is unfortunately the only readily-available data source regarding breastfeeding rates in Seychelles. For further information, see www.breastfeeding-mercury.info.
57g) Rice and Barrone, Critical Periods of Vulnerability for the Developing Nervous System: Evidence from Humans and Animal Models, EPA National Center for Environmental Assessment, 2000,at www.ncbi.nlm.nih.gov/pmc/articles/PMC1637807
58a) Korrick et al., Polychlorinated Biphenyls (PCBs), Organochlorine Pesticides, and Neurodevelopment, Current opinion in pediatrics, at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3878996/
58b) Myers et al., Effects of prenatal methylmercury exposure from a high fish diet on developmental milestones in the Seychelles Child Development Study, Neurotoxicology. 1997;18(3):819-29. at http://www.ncbi.nlm.nih.gov/pubmed/9339828;
van Wijngaarden et al., Prenatal methyl mercury exposure in relation to neurodevelopment and behavior at 19 years of age in the Seychelles Child Development Study, Neurotoxicol Teratol. 2013 Sep-Oct;39:19-25. doi: 10.1016/j.ntt.2013.06.003. Epub 2013 Jun 14. at http://www.ncbi.nlm.nih.gov/pubmed/23770126
59) Debes F et al., Impact of prenatal methylmercury exposure on neurobehavioral function at 14 years. Neurotoxicol Teratol. 2006 May-Jun;28(3):363-75. Epub 2006 May 24 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1543702/
60) Gary J. Myers et al., Postnatal Exposure to Methyl Mercury from Fish Consumption: a Review and New Data from the Seychelles Child Development Study (Table 2) Neurotoxicology. 2009 May; 30(3): 338–349. Published online 2009 January 21. doi: 10.1016/j.neuro.2009.01.005 PMCID: PMC2743883 NIHMSID: NIHMS119840 at www.ncbi.nlm.nih.gov/pmc/articles/PMC2743883).
60a) The summary chart in Myers et al. indicated an age range of 0.5 to 6 in the entry for the Cordier study, but that was incorrect; the Cordier study’s only evaluation of children’s postnatal mercury exposures was done with children aged 5 to 12. (In that study,61 see p. 2, top right, and p. 7.) Maternal exposures were the basis for all of the study’s other evaluations. Given the substantial variation in breastfeeding duration in the study population, plus the extent of unknown breastfeeding histories, and the short half-life of mercury in the blood, maternal mercury levels could not be said to be equivalent to child exposures.
60b) See, for example, Julvez et al., Sensitivity of Continuous Performance Test (CPT) at Age 14 Years to Developmental Methylmercury Exposure, Neurotoxicol Teratol. 2010 Nov–Dec; 32(6): 627–632. Published online Aug 10, 2010. doi: PMCID: PMC2980868 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980868
60c) Freire et al., Hair mercury levels, fish consumption, and cognitive development in preschool children from Granada, Spain, Environ Res. 2010 Jan;110(1):96-104. doi: 10.1016/j.envres.2009.10.005 at http://www.ncbi.nlm.nih.gov/pubmed/19909946
61) Cordier et al., Neurodevelopmental Investigations among Methylmercury-Exposed Children in French Guiana Environmental Research Section A 89, 1}11 (2002) doi:10.1006/enrs.2002.4349, available online at www.idealibrary.com at www.unites.uqam.ca/gmf/globalmercuryforum/files/articles/amazon/cordier/cordier_2002.pdf
62) American Academy of Family Physicians website at www.aafp.org/about/policies/all/breastfeeding-support.html
Re allergies: CDC’s Health United States 2011, Table 46, p. 3, at www.cdc.gov/nchs/data/hus/hus11.pdf
Type 2 Diabetes in Children and Young Adults: A “New Epidemic” Francine Ratner Kaufman, MD CLINICAL DIABETES • Volume 20, Number 4, 2002 at http://clinical.diabetesjournals.org/content/20/4/217.full.pdf+html
Re ADHD: see www.breastfeeding-and-ADHD.info for substantial evidence about the time trend of ADHD in the U.S.
Re mental retardation trend: National Center for Health Statistics, Healthy People 2000 Review, 1997. Public Health Service. Lib. of Congress Cat. No. 76-641496, Figure R, found at www.cdc.gov/nchs/data/hp2000/2k97.pdf
Also see www.breastfeeding-health-effects.info, where numerous peer-reviewed studies are cited in support of this statement .
65a) http://www.fda.gov/biologicsbloodvaccines/resourcesforyou/consumers/ucm167471.htm Also Clin Exp Allergy. 2006 April; 36(4): 402–425. Blackwell Publishing Ltd "Too clean, or not too clean: the Hygiene Hypothesis and home hygiene," SF Bloomfield et al. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1448690/ Also Cell Research advance online publication 24 April 2012; doi: 10.1038/cr.2012.65 "Early exposure to germs and the Hygiene Hypothesis" Dale T Umetsu Division of Immunology, Karp Laboratories, Children's Hospital Boston, Harvard Medical School, Boston,MA http://www.nature.com/cr/journal/vaop/ncurrent/full/cr201265a.html
Also, "About Allergies/ Why Are Allergies Increasing?" at http://fooddrugallergy.ucla.edu/body.cfm?id=40
66) Jens Walkowiak et al., Environmental exposure to polychlorinated biphenyls and quality of the home environment: effects on psychodevelopment in early childhood. Lancet 2001: 358: 1602-07 Abstract at www.thelancet.com/journals/lancet/article/PIIS0140-6736(01)06654-5/abstract
66a) Mocarelli et al., Perinatal Exposure to Low Doses of Dioxin Can Permanently Impair Human Semen Quality, Environ Health Perspect. May 2011; 119(5): 713–718. Published online Jan 24, 2011. doi: 10.1289/ehp.1002134 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3094426/
66c) Jacobson JL, Jacobson SW, Humphrey HEB. 1990a. Effects of in utero exposure to polychlorinated biphenyls and related contaminants on cognitive functioning in young children. J Pediatr 116:38–45. As reported in Schantz et al., Effects of PCB Exposure on Neuropsychological Function in Children, Environmental Health Perspectives • Volume 111 | Number 3 | March 2003, p.371 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1241394/pdf/ehp0111-000357.pdf
66d) G.J. Myers and P.W. Davidson, Does Methylmercury Have a Role in Causing Developmental Disabilities in Children? Environmental Health Perspectives Vol 108, Supplement 3 June 2000 at www.ncbi.nlm.nih.gov/pmc/articles/PMC1637830/pdf/envhper00312-0050.pdf
66e) Lind et al., Breastfeeding and Later Psychosocial Development of Children at 6 Years of Age, Pediatrics Vol. 134 No. Supplement 1 September 1, 2014, pp. S36 -S41 (doi: 10.1542/peds.2014-0646G) at http://pediatrics.aappublications.org/content/134/Supplement_1/S36.full, citing Breastfeeding and subsequent social adjustment in six- to eight-year-old children. J Child Psychol Psychiatry. 1987;28(3):379–386pmid:3597562
67) Schantz et al., Effects of PCB Exposure on Neuropsychological Function in Children Environmental Health Perspectives, Vol. 111, p. 367, at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1241394/pdf/ehp0111-000357.pdf p. 363
68) Gascon et al., Polybrominated Diphenyl Ethers (PBDEs) in Breast Milk and Neuropsychological Development in Infants US National Library of Medicine National Institutes of Health Environ Health Perspect v.120(12); Dec 2012 > PMC3548276 Environ Health Perspect. 2012 December; 120(12): 1760–1765. at www.ncbi.nlm.nih.gov/pmc/articles/PMC3548276
68a) Cheuk et al., Attention-Deficit Hyperactivity Disorder and Blood Mercury Level: a Case-Control Study in Chinese Children Neuropediatrics 2006; 37: 234–240 at http://www.uni-kiel.de/medinfo/material/seminar_ws0809/Artikel%20Statistische%20Modelle%20WS%202008_09.pdf
68b) R.C. Gupta, Ed., Reproductive and Developmental Toxicology, Burlington : Elsevier Science, 2011, ISBN: 978-0-12-382032-7, at http://www.sciencedirect.com/science/book/9780123820327.
68c) Peterson et al., Effects of Prenatal Exposure to Air Pollutants (Polycyclic Aromatic Hydrocarbons) on the Development of Brain White Matter, Cognition, and Behavior in Later Childhood, JAMA Psychiatry. Published online March 25, 2015. doi:10.1001/jamapsychiatry.2015.57 at http://archpsyc.jamanetwork.com/article.aspx?
68d) Main et al. Flame retardants in placenta and breast milk and cryptorchidism in newborn boys. Environ Health Perspect. 2007 Oct;115(10):1519–1526. (Note that “newborn” includes the first 28 days after birth (medical-dictionary.thefreedictionary.com/newborn), and that cryptorchidism can be acquired after birth.)
68e) Herbstman et al., Developmental Exposure to Polybrominated Diphenyl Ethers and Neurodevelopment. Curr Environ Health Rep. 2014 Jun 1;1(2):101-112. at http://www.ncbi.nlm.nih.gov/pubmed/25530937.
68f) .Costa et al., Developmental neurotoxicity of polybrominated diphenyl ether (PBDE) flame retardants. Neurotoxicol. 2007;28(6):1047–67.
69) Larssona et al., Associations between indoor environmental factors and parental-reported autistic spectrum disorders in children 6–8 years of age NeuroToxicology Volume 30, Issue 5, September 2009, Pages 822–831
70) Mascola,et al., Exposure of young infants to environmental tobacco smoke: breast-feeding among smoking mothers. Am J Public Health. 1998 June; 88(6): 893–896. PMCID: PMC1508233 found at www.ncbi.nlm.nih.gov/pmc/articles/PMC1508233
70a) Perinatal Air Pollutant Exposures and Autism Spectrum Disorder in the Children of Nurses’ Health Study II Participants, Roberts et al., published June, 2013 in Environmental Health Perspectives, at http://ehp.niehs.nih.gov/1206187)
70b) His HC et al.,The neurological effects of prenatal and postnatal mercury/methylmercury exposure on three-year-old children in Taiwan, Chemosphere. 2014 Apr;100:71-6. doi: 10.1016/j.chemosphere.2013.12.068. Epub 2014 Jan 23. at http://www.ncbi.nlm.nih.gov/pubmed/24461425
70c) Oken et al., Maternal fish intake during pregnancy, blood mercury, and child cognition at age 3 years in a US cohort, Am J Epidemiol, May 2008 PMCID: PMC2590872 NIHMSID: NIHMS74985 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2590872
70d) Jedrychowski et al., Effects of prenatal exposure to mercury on cognitive and psychomotor function in one-year-old infants: epidemiologic cohort study in Poland, Ann Epidemiol, 2006 Jun;16(6):439-47. Epub 2005 Nov 7. at http://www.ncbi.nlm.nih.gov/pubmed/16275013
70e) Quote from Heather Patisaul, biology professor at North Carolina State University who is studying the effect of endocrine-disrupting compounds, in “A Threat to Male Fertility” in New York Times, Mar. 21, 2014, at http://well.blogs.nytimes.com/2014/03/21/a-threat-to-male-fertility/?_php=true&_type=blogs&_r=0
70f) See footnotes 6, 15, and 29 (Nataf, et al., Bradstreet et al., and DeSoto et al.) in D. Austin, An epidemiological analysis of the ‘autism as mercury poisoning’ hypothesis’, International Journal of Risk and Safety in Medicine, 20 (2008) 135-142 at http://researchbank.swinburne.edu.au/vital/access/manager/Repository/swin:9302 Also see Geier DA et al., Blood mercury levels in autism spectrum disorder: Is there a threshold level? Acta Neurobiol Exp (Wars). 2010;70(2):177-86, www.ncbi.nlm.nih.gov/pubmed/20628441.
70g) Stringari et al., Postnatal Methylmercury Exposure Induces Hyperlocomotor Activity and Cerebellar Oxidative Stress in Mice: Dependence on the Neurodevelopmental Period, Neurochemical Research April 2006, Volume 31, Issue 4, pp 563-569 at http://link.springer.com/article/10.1007/s11064-006-9051-9
70h) Yokoo et al., Low level methylmercury exposure affects neuropsychological function in adults, Environ Health. 2003; 2: 8. Published online Jun 4, 2003. doi: PMCID: PMC165591at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC165591
70i) Lucchini et al., Neurotoxic effect of exposure to low doses of mercury, Med. Lav, 2002, at http://www.ncbi.nlm.nih.gov/pubmed/12197270
70k) Carta et al., Sub-clinical neurobehavioral abnormalities associated with low level of mercury exposure through fish consumption, Neurotoxicology. 2003 Aug;24(4-5):617-23, at http://www.ncbi.nlm.nih.gov/pubmed/12900074
and in a dose-effect relationship:-- Carta et al., Neuroendocrine and neurobehavioral effects associated with exposure to low doses of mercury from habitual consumption of marine fish, Med Lav. 2002 May-Jun;93(3):215-24. at http://www.ncbi.nlm.nih.gov/pubmed/12197271
70n) Davidson et al., Fish Consumption, Mercury Exposure, and Their Associations with Scholastic Achievement in the Seychelles Child Development Study, Neurotoxicology. Author manuscript; available in PMC Sep 1, 2011, Published in final edited form as:Neurotoxicology. Sep 2010; 31(5): 439–447. Published online May 31, 2010. doi: 10.1016/j.neuro.2010.05.010, PMCID: PMC2934742 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2934742/
71) Banaschewski et al., Autism and ADHD across the life span. Differential diagnoses or comorbidity? Nervenarzt. 2011 May;82(5):573-80. doi: 10.1007/s00115-010-3239-6. [Article in German] at www.ncbi.nlm.nih.gov/pubmed/21484168
71a) Stewart P et al., Response inhibition at 8 and 9 1/2 years of age in children prenatally exposed to PCBs, Neurotoxicol Teratol. 2005 Nov-Dec;27(6):771-80. Epub 2005 Sep 28, at http://www.ncbi.nlm.nih.gov/pubmed/16198536
71b) Stewart PW, Response inhibition during Differential Reinforcement of Low Rates (DRL) schedules may be sensitive to low-level polychlorinated biphenyl, methylmercury, and lead exposure in children, Environ Health Perspect. 2006 Dec;114(12):1923-9, at http://www.ncbi.nlm.nih.gov/pubmed/17185286
71c) Boucher et al., Response Inhibition and Error Monitoring during a Visual Go/No-Go Task in Inuit Children Exposed to Lead, Polychlorinated Biphenyls, and Methylmercury, Environ Health Perspect. Apr 2012; 120(4): 608–615 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339450
71d) Wright et al., Association of Prenatal and Childhood Blood Lead Concentrations with Criminal Arrests in Early Adulthood, Published online May 27, 2008. doi: 10.1371/journal.pmed.0050101 PMCID: PMC2689664 PLoS Med. May 2008; 5(5): e101
71e) Lackmann, Human Milk, Environmental Toxins and Pollution of Our Infants: Disturbing Findings during the First Six Months of Life, Int J Biomed Sci. Jun 2006; 2(2): 178–183, at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614598.
72) Gascon M. et al., Effects of pre and postnatal exposure to low levels of polybromodiphenyl ethers on neurodevelopment and thyroid hormone levels at 4 years of age Environ Int. 2011 Apr;37(3):605-11. doi: 10.1016/j.envint.2010.12.005. Epub 2011 Jan 14 found at www.ncbi.nlm.nih.gov/pubmed/21237513)
72a) Giordano et al., Developmental Neurotoxicity: Some Old and New Issues, ISRN Toxicol. 2012; 2012: 814795, PMCID: PMC3658697 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3658697
73) S Patandin et al., Effects Of Environmental Exposure To Polychlorinated Biphenyls And Dioxins On Growth And Development In Young Children: A Prospective Follow-Up Study Of Breast-Fed And Formula-Fed Infants From Birth Until 42 Months Of Age Table 7.5 and accompanying text. at http://Repub.Eur.Nl/Res/Pub/19721
74) Kate Hoffman, et al., Lactational Exposure to Polybrominated Diphenyl Ethers and Its Relation to Social and Emotional Development among Toddlers Environ Health Perspect. 2012 October; 120(10): 1438–1442. Published online 2012 July 19. doi: 10.1289/ehp.1205100 PMCID: PMC3491946 at www.ncbi.nlm.nih.gov/pmc/articles/PMC3491946
75) Katharina M. Main et al., Human Breast Milk Contamination with Phthalates and Alterations of Endogenous Reproductive Hormones in Infants Three Months of Age, Environ Health Perspect. 2006 February; 114(2): 270–276. Published online 2005 September 7. doi: 10.1289/ehp.8075 PMCID: PMC1367843 at http://www.ncbi.nlm.nih.gov/pubmed/16451866
76) Mortensen GK, et al., “Determination of phthalate monoesters in human milk, consumer milk, and infant formula by tandem mass spectrometry (LC-MS-MS),” Anal Bioanal Chem, 382(4):1084-92, 2005. at http://link.springer.com/article/10.1007%2Fs00216-005-3218-0
77) Hertz-Picciotto et al., Prenatal exposures to persistent and non-persistent organic compounds and effects on immune system development, Basic Clin Pharmacol Toxicol. 2008 Feb;102(2):146-54. doi: 10.1111/j.1742-7843.2007.00190.x. at www.ncbi.nlm.nih.gov/pubmed/18226068
Also see Dietert and Dietert, Potential for Early-Life Immune Insult Including Developmental Immunotoxicity in Autism and Autism Spectrum Disorders, Journal of Toxicology and Environmental Health, Part B: Critical Reviews, 11:8, 660-680 http://dx.doi.org/10.1080/10937400802370923
78) U.S. Agency for Toxic Substances and Disease Registry, Toxicological Profile for Polychlorinated Biphenyls (PCBs), 2000, at http://www.atsdr.cdc.gov/toxprofiles/tp17.pdf; this document refers to studies (see pp. 560 and 573) providing data about PCB levels in breast milk and in formula; a major difference in PCB levels of breastfed vs. formula-fed children at 3 ½ years was found in Lanting et al. (1998a), p. 569,and is compatible with data referred to above.
79) U.S. ATSDR website at http://www.atsdr.cdc.gov/csem/csem.asp?csem=7&po=9 regarding lead, and 58 regarding mercury.
80) Blaurock-Busch et al.,Toxic Metals and Essential Elements in Hair and Severity of Symptoms among Children with Autism Maedica (Buchar). Jan 2012; 7(1): 38–48. PMCID: PMC3484795 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484795/
80a) Rossignol et al., Environmental toxicants and autism spectrum disorders: a systematic review Transl Psychiatry. Feb 2014; 4(2): e360. Published online Feb 11, 2014. at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944636/
81) See “Phthalates in PVC Plastics” at http://www.astm.org/standardization-news/update/phthalates-in-pvc-plastics-so13.html
81a) Mocarelli et al., Perinatal Exposure to Low Doses of Dioxin Can Permanently Impair Human Semen Quality, Environ Health Perspect. May 2011; 119(5): 713–718. Published online Jan 24, 2011. doi: 10.1289/ehp.1002134 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3094426/
82) Figure 1 and text above it in Boucher et al., Response Inhibition and Error Monitoring during a Visual Go/No-Go Task in Inuit Children Exposed to Lead, Polychlorinated Biphenyls, and Methylmercury, Environ Health Perspect. Apr 2012; 120(4): 608–615 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339450
83) Bernard Weiss, Vulnerability of Children and the Developing Brain to Neurotoxic Hazards, Environmental Health Perspectives * Vol 108, Supplement 3 * June 2000 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1637834/pdf/envhper00312-0016.pdf
83a) Eskenazi B, Marks AR, Bradman A, Fenster L, Johnson C, Barr DB, et al. 2006. In utero exposure to dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) and neurodevelopment among young Mexican American children. Pediatrics 118(1):233–241
Eskenazi B, Marks AR, Bradman A, Harley K, Barr DB, Johnson C, et al. 2007. Organophosphate pesticide exposure and neurodevelopment in young Mexican-American children. Environ Health Perspect 115:792–798; doi: 10.1289/ehp.9828
83b) Curtis et al., Chronic Metals Ingestion By Prairie Voles Produces Sex-Specific Deficits In Social Behavior: An Animal Model Of Autism, Behav Brain Res. 2010 Nov 12; 213(1): 42–49. Published online 2010 Apr 28. doi: 10.1016/j.bbr.2010.04.028 PMCID: PMC2880538 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2880538/
83c) EM Roberts et al., Maternal residence near agricultural pesticide applications and autism spectrum disorders among children in the California Central Valley, Environ Health Perspect. 2007 Oct;115(10):1482-9, at http://www.ncbi.nlm.nih.gov/pubmed/17938740/ “comparing children of mothers living within 500 m of field sites with the highest nonzero quartile of organochlorine poundage to those with mothers not living near field sites suggested an odds ratio for ASD of 6.1 (95% confidence interval, 2.4-15.3”
83d) Roberts and English, Bayesian modeling of time-dependent vulnerability to environmental hazards: an example using autism and pesticide data, Statistics in Medicine, Published online 7 September 2012 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/sim.5600
83e) .Eskenazi and seven others, Organophosphate Pesticide Exposure and Neurodevelopment in Young Mexican-American Children, Environ Health Perspect. 2007 May; 115(5): 792–798. PMCID: PMC1867968, Table 5, at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1867968/
84) U.S. Census Bureau data, 2012.
85) See footnotes 6, 15, 16, and 29 in D. Austin, An epidemiological analysis of the ‘autism as mercury poisoning’ hypothesis’, International Journal of Risk and Safety in Medicine, 20 (2008) 135-142 at http://researchbank.swinburne.edu.au/vital/access/manager/Repository/swin:9302
Also Adams JB et al., Biol Trace Elem Res. 2013 Feb;151(2):171-80. doi: 10.1007/s12011-012-9551-1. Epub 2012 Nov 29.Toxicological status of children with autism vs. neurotypical children and the association with autism severity. at http://www.ncbi.nlm.nih.gov/pubmed/23192845
Also Geier DA et al., Blood mercury levels in autism spectrum disorder: Is there a threshold level? Acta Neurobiol Exp (Wars). 2010;70(2):177-86, http://www.ncbi.nlm.nih.gov/pubmed/20628441
86) Eskenazi B et al., In utero and childhood polybrominated diphenyl ether (PBDE) exposures and neurodevelopment in the CHAMACOS study Environ Health Perspect. 2013 Feb;121(2):257-62. doi: 10.1289/ehp.1205597. Epub 2012 Nov 7 at http://ehp.niehs.nih.gov/1205597
87) Roberts et al., Perinatal Air Pollutant Exposures and Autism Spectrum Disorder in the Children of Nurses’ Health Study II Participants, published June, 2013 in Environmental Health Perspectives, at http://ehp.niehs.nih.gov/1206187/)
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