A strong risk factor for autism, about which something can be done

(This article under construction) by DP Meulenberg

Summary and contents:

Introduction: (summary): One risk factor for autism has been found that is (a) not much less strong than being an identical twin and (b) far stronger than all of the other risk factors, with a 40-fold increased risk.. At the same time, there is considerable scientific evidence indicating that this specific risk is much greater for males than for females, which is compatible with the male-female ratio of autism prevalence. And there is also reason to think that measures can be taken that could significantly minimize the effects of this risk factor, including one as simple as supplements of vitamin E administered to developing infants.

Section 1.a: (summary): Abnormalities in the cerebellum are detectable when ASD symptoms are first detected. There is substantial evidence from many sources, and from many different types of sources, that supports the statement to the effect that harm to the cerebellum dramatically increases the risk for autism. For complete text of this section, go to Section 1.a

Section 1.b: (summary): Reductions in separate subregions of the cerebellum have been found to correlate with severity of specific symptoms of ASD. For complete text of this section, go to Section 1.b.

Section 2: (summary): Neurological development is vulnerable to effects of environmental toxins. Research from multiple laboratories has demonstrated that neurological toxins among those with autism are higher than among typically-developing children. The focus of the rest of this article will be on two neurological toxins (PCBs and dioxins) to which infants are exposed far beyond established safe doses; these are exposures that, by good evidence, are likely to be damaging the cerebellum and thereby leading to autism, and which could also be greatly reduced. Both of these toxins first came to be widespread in the U.S. environment in the middle of the 20th century, and increases in autism came after that.

Section 2.a (summary): PCBs are ranked by the U.S. ATSDR as being among the top 5 priority hazardous substances. According to the EPA, "the overall evidence supports a concern for effects of PCBs on children’s neurological development." Considerable evidence indicates that PCBs are associated with deficits in IQ, memory, language, school performance, and social behavior. Several experiments have indicated that PCBs and related compounds (which include dioxins) may cause brain damage. Dioxins have proven to be developmentally toxic, immunotoxic and neurotoxic.

Exposures of children living near incinerators, emissions from which contain PCBs and dioxins, have been closely linked with ASD-like symptoms. Proximity to traffic pollution, which has been found to contain major amounts of PCBs and dioxins, has been strongly associated with ASD diagnoses. PCBs have been found to reduce cerebellar cells in a dose-dependent manner.

For complete text of the above section, go to Section 2.a.

Section 2.b: (summary): Exposures to pesticides, which normally contain dioxins, are a strong risk factor for autism. Autism prevalence was found to be six times as high as normal near California agricultural fields where organochlorine pesticides were applied; autism prevalence varied in correlation with distance from the fields and with poundage of pesticides applied. Dioxins are apparently present in most, possibly all, major pesticides; this may account for the strong link of autism with exposures to pesticides, especially since many of those formulations specifically target the nervous system. For complete text of this section, go to Section 2.b.

Section 3: (Summary): PCBs and dioxins have greater effects on males than on females, which makes them especially compatible as causes of autism..

Section 4: (Summary): The period of greatest sensitivity, especially of the cerebellum, to effects of toxins is the first year after birth.

Section 5: (Summary): The period of greatest exposure to PCBs and dioxins is also the first year after birth. This means that those toxins are especially compatible with being causes of damage to the cerebellum.

Section 6: (Summary): There is one predominant source of exposure of the developing cerebellum to PCBs and dioxins at its stage of greatest sensitivity

Section 7: (Summary): What can be done to minimize the effects of the exposures to PCBs and dioxins, or to minimize the exposures per se?

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Introduction:

Many risk factors for autism have been identified; but the risk for almost all of those factors is fairly small, and there is normally little or nothing that can be done to minimize those risks, in any case. (For a fairly recent review of many risk factors for autism, see the 2017 meta-analysis at www.ncbi.nlm.nih.gov/pmc/articles/PMC5419910/.) However, one risk factor (harm to the cerebellum) has been found that is (a) not much less strong than being an identical twin and (b) far stronger than all of the other risk factors. And there is good reason to believe that effects related to this risk factor could be greatly reduced.

There is considerable evidence that indicates harm to the cerebellum as a factor that leads to traits of autism (Section 1). Two developmental toxins, PCBs and dioxins, have been found to harm neurological development in general and the cerebellum in particular (Section 2). Those toxins both have greater effects on males than on females, which makes them especially compatible as causes of autism (Section 3). The first year after birth is the time when the cerebellum is especially sensitive to effects of toxins (Section 4). The first year after birth is also the period of greatest exposure to both PCBs and dioxins (Section 5). And measures could reasonably be taken that could significantly minimize the harm to the cerebellum caused by these toxins (Section 6).

Section 1: Harm to the cerebellum stands out as a risk factor for autism.

There is substantial evidence from many different sources, and from many different types of sources, that supports the statement to the effect that harm to the cerebellum is an outstanding risk factor for autism.

Section 1.a: Strong evidence from three separate research teams implicating damage to the cerebellum as causing autism:

1.a.1: A 2017 study (McCarthy and Wright)¹ states it in detailed and scientific terms: "Evidence from post-mortem histology, genetics, animal models, imaging and clinical studies of ASD implicate the cerebellum in both the etiology and manifestation of the behavioral phenotype ...... Damage to the cerebellum in infancy is among the highest risk factors for developing ASD (estimated 40 fold increase), second only to having an identical twin with autism...." The source that the authors cited for the 40-fold increased risk of autism with cerebellar damage was a 2007 study in the journal Pediatrics, by a team of 12 researchers.²

1.a.2: Another research team (Wang et al., 2014³) arrived at a similar figure (36-fold increase) for autism risk in relation to cerebellar injury. Those authors further stated that "damage to the hemispheres (of the cerebellum) results in language delay and visual and verbal reasoning deficits, and damage to the vermis (of the cerebellum) results in withdrawn social behavior, impaired gaze, anxiety, and stereotyped behavior."

Going into the time of vulnerability to the damage being discussed, the Wang et al. authors describe various findings indicating that "persistent cerebellar volume differences emerge starting in the first two years of life." The authors summarize, "starting from the earliest ages when core ASD deficits appear, the cerebellum shows both gross and cellular defects...." So the first signs of detectable cerebellar defects that are of concern regarding autism are seen to start appearing well into the postnatal period -- "when core ASD deficits appear."

(It is worthwhile noting the distinctly postnatal timing of the earliest indications of autism-related damage to the cerebellum, since there is a widespread notion to the effect that only prenatal harm is sufficiently important to justify attention.)

Going into detail about a causal connection between cerebellar defects and autism, the Wang et al. authors describe a laboratory experiment that they say provided an important demonstration that early-life cerebellar development can play a necessary role in acquiring core social capacities. The authors refer to that study as providing "demonstration that cerebellum-specific insult is sufficient to generate ASD-like symptoms." It is of special interest here that, in place of the usual cautious wording that is typical in scientific studies, including "suggests that" and "might" (have a certain effect), these authors used stronger wording: "demonstration that cerebellum-specific insult is sufficient to generate ASD-like symptoms." That expression of certainty is reasonable given that the conclusion is based on an experimental trial, investigating cerebella and behavior in animals under controlled laboratory conditions, as opposed to being based solely on observations of the complex human world; the many confounders that are known to normally be present in studies of humans prevent strong conclusions of cause and effect. (The lead author of this study was Samuel S.-H. Wang of the Princeton Neuroscience Institute and the Department of Molecular Biology, Princeton University.)

For considerable additional evidence of the relationship between harm to the cerebellum and autism, go to Appendix A.

1.a.3: For the third set of strong evidence implicating damage to the cerebellum as causing autism, note the following: According to an article in the American Journal of Psychiatry (Allen and Courchesne, 2003), "over 90% of autistic cerebella examined at autopsy have shown well-defined cerebellar anatomic abnormalities.”⁴ Several other studies by other research teams support the same general conclusion of the centrality of the cerebellum to autism <<Gadad et al., Neuropathology and Animal Models of Autism: Genetic and Environmental Factors, Autism Res Treat. 2013; 2013: 731935 PMCID: PMC3787615 at www.ncbi.nlm.nih.gov/pmc/articles/PMC3787615

Hashimoto et al., Development of the brainstem and cerebellum in autistic patients, J Autism Dev Disord. 1995 Feb;25(1):1-18. at www.ncbi.nlm.nih.gov/pubmed/7608030

Rogers et al., Is autism a disease of the cerebellum? An integration of clinical and pre-clinical research, Front Syst Neurosci, 2013, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650713/

.......................................

Any of the findings described in the three subsections above, if considered separately, would be sufficient to justify intense scrutiny of what could be causing harm to the cerebellum during development. The fact that all of those research teams have found harm to the cerebellum to be closely related to autism means that there is special need for consideration of toxins possibly involved in developmental harm to the cerebellum.

To help guide such consideration, it is worth re-stating (from Section 1.a.2) that the cerebellar defects that are so strongly implicated in autism start appearing well into the postnatal period. Also note (later) in Section 4 that the cerebellum's development is especially vulnerable to effects of toxins during the first year after birth.

Section 1.b: Reductions in separate subregions of the cerebellum and in specific tissues of the cerebellum have been found to correlate with ASD or ASD-related symptoms:

According to a 2016 study, it has been found that "the degree of regional and lobular gray matter reductions in different cerebellar subregions correlated with the severity of symptoms in social interaction, communication, and repetitive behaviors."⁵ Those authors also pointed out that "almost all post-mortem analyses of ASD individuals have reported reduced Purkinje cell (specific neurons in the cerebellum) size and number regardless of age, sex, or cognitive ability," citing four other studies as evidence.

Section 2: Vulnerability of neurological development, including autism, to effects of environmental toxins:

According to a 2009 study, "as a whole, recent research from multiple labs is demonstrating that when direct measurements of neurotoxins among those with autism are compared to those without, the levels (of toxins) are higher in those with an ASD." <<DeSoto, Ockham's Razor and autism: The case for developmental neurotoxins contributing to a disease of neurodevelopment, Neurotoxicology, 2009, at https://www.sciencedirect.com/science/article/pii/S0161813X09000746 >>

When summarizing data from 37 unique studies, the authors of a 2014 review article (Rossignol et al.) found that 34 studies (92%) reported an association between estimated exposures to environmental toxicants and ASD. Most of the reviewed studies were said to have had good study designs. ^<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/

The focus of the rest of this article will be on two neurological toxins (PCBs and dioxins) to which infants are exposed far beyond established safe doses; these are exposures that, by good evidence, could damage the cerebellum and lead to autism and could also be greatly reduced.

Both PCBs and dioxins --

-- are known to be neurodevelopmental toxins, with effects found on cerebellar tissues specifically, and with ASD-related effects (evidence will be provided below);

-- first came to be widespread in the U.S. environment in the middle of the 20th century, and increases in autism came after the increases in PCBs and dioxins (details will follow);

-- are ingested by infants in especially high doses during the most sensitive stage of the cerebellum's development (Sections 4 and 5);

-- have greater adverse effects on males than on females (Section 3), a pattern that fits well with the uneven sex ratio in autism prevalence.

-- are ingested by many infants in amounts many times greater than established safe levels (Section 5) ,

PCBs and dioxins rapidly increased in the U.S. environment in the mid-20th century:

PCBs: Production of PCBs (not yet known to be toxic at that time) began in the 1920's but only reached substantial volume after 1945, according to a working group of the International Agency for Research in Cancer; Polychlorinated Biphenyls and Polybrominated Biphenyls, IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, No. 107, IARC Working Group on the Evaluation of Carcinogenic Risk to Humans, 2016, Section 1.3.2, and Table 1.14, at

http://monographs.iarc.fr/ENG/Monographs/vol107/mono107.pdf they were used in various kinds of equipment and in many areas of manual work. Breivik et al., Towards a global historical emission inventory for selected PCB congeners — a mass balance approach: 1. Global production and consumption, Science of Total Environment, Vol. 377, Issues 2-3, May 2007 Exposures increased again in 1949 and later, when PCBs came to be used in various types of building materials. UMassAmherst, Environmental Health and Safety: Polychlorinated Biphenyls (PCBs) - Hazardous Building Materials, at https://ehs.umass.edu/polychlorinated-biphenyls-pcbs-hazardous-building-materials

Dioxins: Burning of plastics is known to emit dioxins to the air. Seltenrich, Incineration Versus Recycling: In Europe, A Debate Over Trash, Yale School of Forestry and Environmental Studies, 2013, at https://e360.yale.edu/features/incineration_versus_recycling__in_europe_a_debate_over_trash

-- Israel Ministry of Environmental Protection: Dangers of Burning Agricultural Waste, at http://www.sviva.gov.il/English/env_topics/AirQuality/Pages/DangersOfBurningWaste.aspx When discussing sources of high concentrations of air pollutants, the Israel Ministry of Environmental Protection states, "The most dangerous emissions can be caused by burning plastics," in large part because of the dioxins produced.

EPA documents substantiate that plastics contained in burning trash are a large part of what produces dioxins when trash is burned (see Appendix D), helping to create the major dioxin emissions that the EPA knows to result from household and farm burning of trash. EPA: An Inventory of Sources and Environmental Releases of Dioxin-Like Compounds in the United States for the Years 1987, 1995, and 2000, EPA/600/P-03/002F November 2006, Table 1-12, at https://cfpub.epa.gov/ncea/dioxin/recordisplay.cfm?deid=159286 ; under Downloads, choose to download the Dioxin Inventory of Sources (Optimized Report). See p. xliv and Section 6.5, "Backyard Barrel Burning." Burning of plastics-containing trash would have became widespread (at least in rural areas) not long after large-scale production of plastics began in the late 1940's; plastics production in the U.S. (especially for consumer goods) expanded "explosively" after the end of World War II (1945), according to a history of plastics in Scientific American. Freinkel: A Brief History of Plastic's Conquest of the World, Scientific American, at https://www.scientificamerican.com/article/a-brief-history-of-plastic-world-conquest/ In line with the above, evidence provided by the ATSDR indicates that dioxin emissions turned upwards in the 1940's. ATSDR dioxin document, Toxicological Profile for Chlorinated Dibenzo-p-Dioxins, 1998, pp. 379 and 391, at https://www.atsdr.cdc.gov/toxprofiles/tp104.pdf

Later decreases but still high levels of PCBs and dioxins: Exposures to both dioxins and PCBs increased for decades and have subsequently declined, but both of those toxins are considered to be "persistent" for good reason and are still present at hazardous levels in U.S. and other environments. A 2010 publication of the Oregon Department of Environmental Quality provided information about high exposures of children to PCBs. Oregon Department of Environmental Quality Environmental Cleanup Program, Oct. 2010, 10-LQ-023, p. D2-4 (attachment 2 of Appendix D, near very end) at

www.oregon.gov/deq/FilterDocs/HumanHealthRiskAssessmentGuidance.pdf Regarding dioxins, many studies finding infants to be commonly exposed to high levels of dioxins were carried out in 2000 and later, decades after environmental emissions of dioxins were reported to be declining. (For a summary on this topic, see Section 3 of www.pollutionaction.org/case-deaton-comment.htm) Note (in the next section) that both PCBs and dioxins are found in traffic pollution, an ongoing or increasing exposure that is in especially close proximity to large segments of the population.

Section 2.a: PCBs and dioxins are probable causes of autism-related damage to the cerebellum.

ace3_neurodevelopmental.pdf

According to the Washington State Department of Ecology, there is considerable evidence indicating that PCBs "impact normal brain development" and "are associated with ... deficits in IQ, memory, language and school performance” and lead to "chronic effects on a range of social and anxiety-related behaviors."<< Washington State Department of Ecology, Multiyear PBT Chemical Action Plan Schedule, 2007, at https://fortress.wa.gov/ecy/publications/documents/0707016.pdf, p. 64. In a 2007 study investigating sources of disruption of production of neurons specifically in the cerebellum, the authors stated, "Several experiments using animal models, including monkeys, have indicated that PCBs and related compounds (dioxins are related to PCBs) may affect TH functions and cause brain damage." <<Kimura-Kuroda et al., Disrupting effects of hydroxy-polychlorinated biphenyl (PCB) congeners on neuronal development of cerebellar Purkinje cells: A possible causal factor for developmental brain disorders?, Chemosphere, 2007, at https://www.sciencedirect.com/science/article/pii/S004565350601647X

Dioxin is referred to as "the most toxic man-made chemical" in an article by an EPA scientist, reviewed in accordance with EPA policy and approved for publication. <L. Birnbaum, Endocrine Effects of Prenatal Exposure to PCBs, Dioxins, and Other Xenobiotics: Implications for Policy and Future Research, Env Health Perspec,

Volume 102, Number 8, August 1994 at https://ehp.niehs.nih.gov/doi/10.1289/ehp.94102676

Dioxins have proven to be developmentally toxic, immunotoxic and neurotoxic, according to highly-published scientists with the EPA and the NIH. White and Birnbaum, An Overview of the Effects of Dioxins and Dioxin-like Compounds on Vertebrates, as Documented in Human and Ecological Epidemiology, J Environ Sci Health C Environ Carcinog Ecotoxicol Rev, 2000, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2788749/ The Minnesota Pollution Control Agency says that health effects of dioxins have been detected in humans at levels of less than one part per trillion, and the average level in U.S humans has been found to be over 20 times higher than that, as of the 1990's. Minnesota Pollution Control Agency: If you're burning garbage, you're making poison,at https://www.pca.state.mn.us/sites/default/files/w-hhw1-17.pdf Among breastfed children in areas of Vietnam with elevated levels of dioxins (remaining from the decades-earlier war years), the most highly-exposed group showed significantly higher Autism Spectrum Rating Scale scores than the mildly-exposed groups, even while showing no differences in neurodevelopmental scores. << Nishijo et al., 2,3,7,8-Tetrachlorodibenzo-p-dioxin in breast milk increases autistic traits of 3-year-old children in Vietnam, Mol Psychiatry, 2014, at https://www.ncbi.nlm.nih.gov/pubmed/24637425

Probable PCB and dioxin exposures near incinerators have been closely linked with ASD-like symptoms:

Authors of a 2013 study in Taiwan (Lung et al.<<Lung et al., Incinerator Pollution and Child Development in the Taiwan Birth Cohort Study, Int. J. Environ. Res. Public Health 2013, especially p. 2251 and the Supplemental Materials, at www.mdpi.com/1660-4601/10/6/2241/pdf ;

"...children living near an incinerator who were breastfed had an increased risk of U/DDD compared with those who did not live near incinerators.."

>> worked with data from over 21,000 children, 953 of whom lived within three kilometers of a municipal incinerator. The study reported about effects of local incinerators on autism-related developmental outcomes in children, as indicated by parental responses to questions. Among children who lived within the designated distance from the incinerators and who had been breastfed for at least six months, adverse effects associated with the local incinerator on measured outcomes were reported to be highly significant in all four developmental areas that were asked about, areas that were related to symptoms of ASD: << See list of symptoms of ASD at http://www.autismkey.com/autism-symptoms/ >> gross motor development, fine motor development, language, and social development. When discussing the relationships between incinerator emissions and adverse effects on neurological development, the authors referred to dioxins, PCBs, and mercury as having been found to be significantly present in incinerator emissions, and cited two studies as having reported about dioxins in milk of women living near incinerators. (The usual socio-economic differences that affect which families typically live closer to waste facilities were said by the authors to be reversed in Taiwan, such that they would not account for the worse outcomes of children living near incinerators.)

Proximity to traffic pollution, probably including PCBs and dioxins, has been strongly linked with ASD:

A 2013 study (Volk et al.) found a high odds ratio (3.1) for autism linked with postnatal exposures received from residence during the first year of life in areas in the top quartile of traffic-related pollution, compared with controls. <<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> This, also, is related to probable effects of PCBs and dioxins in relation to risk of autism, since both toxins are present in vehicle emissions.<< Lien-Te Hsieh et al., Reduction of Toxic Pollutants Emitted from Heavy-duty Diesel Vehicles by Deploying Diesel Particulate Filters, Aerosol and Air Quality Research, 11: 709–715, 2011, at http://aaqr.org/VOL11_No6_November2011/8_AAQR-11-05-OA-0058_709-715.pdf>>,

Also U.S. National Library of Medicine, Toxtown, Persistent Organic Pollutants (POPs), at http://toxtown.nlm.nih.gov/text_version/chemicals.php?id=86>> In a 2013 U.S. study, PCB concentrations were found to be about five times as high in carpet dust in homes within 546 meters from major roads as they were in homes that were over 1000 meters from those roads; the p-value for this finding was <.01, indicating a high level of statistical significance. ^< DellaValle et al., Environmental determinants of polychlorinated biphenyl concentrations in residential carpet dust, Environ Sci Technol. 2013 Sep 17; 47(18): 10405–10414. at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076890>> In a study in Colombia, measurements of PCBs (as well as dioxins) taken near vehicular sources were found to be almost six times as high as measurements made over a mile farther away.Cortés et al., PCDD/PCDF and dl-PCB in the ambient air of a tropical Andean city: passive and active sampling measurements near industrial and vehicular pollution sources, Sci Total Environ. <#> 2014 Sep 1 at https://www.ncbi.nlm.nih.gov/pubmed/24555963 Note that PCDD/F is a designation for what is more commonly referred to as dioxins.

In a study in Sweden, concentration of PCBs in ambient air pollution samples "decreased with increasing distance to the urban centre of Stockholm;" concentrations of each of the two basic types of PCBs declined more than 90% over the transition of sampling from urban center to outlying areas; the authors' focus in this sampling was on vehicular emissions. Ishaq et al., PCBs, PCNs, PCDD/Fs, PAHs and Cl-PAHs in air and water particulate samples--patterns and variations, in Chemosphere March 2003 at https://www.researchgate.net/publication/10934371_PCBs_PCNs_PCDDFs_PAHs_and_Cl-PAHs_in_air_and_water_particulate_samples--patterns_and_variations Their highest readings for PCBs (and other toxins) were at locations of unusually high vehicular emissions (road tunnels), and there were decreases in PCB concentrations with increasing distance outbound from concentrated traffic emissions.

Dioxins: A 2009 Czech study found "dramatic decreases" in concentrations of pollutants (including dioxins) in soil with increasing distances from roadways. Concentrations next to roadways were found to be as high as in industrially-polluted areas. Concentrations of dioxins were found to be continuing to decrease, stepwise, with progressive distances from roadways up to the last distance measured (100 meters); in measurements at four different locations at the farthest distance, the concentrations were only 2% to 6% as high as next to the roadways.^66hŠtěpánková et al., Dioxin-Like and Endocrine Disruptive Activity of Traffic-Contaminated Soil Samples, Arch Environ Contam Toxicol (2009), at https://www.researchgate.net/publication/26259547_Dioxin-Like_and_Endocrine_Disruptive_Activity_of_Traffic-Contaminated_Soil_Samples; specifically, Table 3, 1st column re dioxins.

So autism diagnoses have been found to be strongly correlated with proximity to major roads, and the recognized neurodevelopmental toxins, PCBs and dioxins, have both been found to be many times higher than normal close to major roads. That should be seen together with considerable other evidence, presented here, linking autism with PCB and dioxin exposures.

Effects of PCBs and dioxins on the cerebellum, specifically; and a possible way to counteract adverse effects of PCBs:

When discussing effects of exposure to dioxin, authors of a 2005 study (Williamson et al.) point out that multiple studies report "functional abnormalities consistent with improper cerebellar maturation" as results of dioxin exposure. Williamson et al., Aryl Hydrocarbon Receptor Expression and Activity in Cerebellar Granule Neuroblasts: Implications for Development and Dioxin Neurotoxicity, Toxicological Sciences, Volume 83, Issue 2, 1 February 2005, at https://academic.oup.com/toxsci/article/83/2/340/1713944

-- Also Kim and Yang, Neurotoxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in cerebellar granule cells, EXPERIMENTAL and MOLECULAR MEDICINE, Vol. 37, 2005, at https://www.nature.com/articles/emm20058.pdf?origin=ppub

Note that the above was not merely a general statement about wide-ranging toxicity; those findings have apparently been rather specific with regard to (a) dioxin's effect on the cerebellum, and (b) development as the stage of principal concern for the cerebellum, regarding dioxin exposure. Considering that early injury to the cerebellum has been found to be an outstandingly strong risk factor for autism (see Section 1), these studies would seem to provide good reason to focus on dioxin as a causal agent related to autism.

A 2010 experiment with rat cerebellar tissue found that exposures to four out of six types of PCBs reduced cerebellar cells, and did so in a dose-dependent manner. The author pointed out that compatible findings of toxicity of certain types of PCBs in relation to cerebellar cells were reported in another study (Tan et al., Ortho-Substituted but Not Coplanar PCBs Rapidly Kill Cerebellar Granule Cells, Toxicological Sciences, 2004, at https://academic.oup.com/toxsci/article/79/1/147/1654028). Administration of vitamin E along with the PCBs greatly increased the survival rate of the cerebellar cells. <<Bernsten, Neurotoxic effects on cerebellar granule cells and induction of ROS formation in human neutrophil granulocytes after exposure to polychlorinated biphenyls and penitrem A (pp. 50-53, 84), Dept. of Biology, University of Oslo, 2010, at https://www.duo.uio.no/bitstream/handle/10852/11804/Berntsen.pdf?sequence=1&isAllowed=y

For other evidence about adverse effects of these toxins on the developing brain and on the cerebellum specifically, see Appendix B and Section 3.

Section 2.b: Pesticides, which typically contain dioxins, are a strong risk factor for autism.

The authors of the Rossignol review said that “the toxicants that appeared to have the strongest association with ASD were pesticides and air pollutants.”

The author of the article quoted at the beginning of this section (DeSoto, 2009) pointed out that the study to be referred to below qualified as meeting "the gold standard" for testing whether early exposures to environmental toxins play an important role in causing neurodevelopmental harm: by measuring the variable of concern prospectively (pesticide exposures, in this case) and then following the participants to see if measured levels will predict who later develops the outcome of interest. Higher levels of pesticide metabolites did successfully predict significantly higher risk of pervasive developmental disorder, in the study cited by the author. Also, in a 2007 study, autism prevalence was found to be six times as high as normal near California agricultural fields where organochlorine pesticides were applied; autism prevalence varied in correlation with distance from the fields and with poundage of pesticides applied. << 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)”>> A follow-up study found that the time of peak correlation of pesticide exposure with autism incidence in the above study was in the year after birth. << Roberts and English, Bayesian modeling of time-dependent vulnerability to environmental hazards: an example using autism and pesticide data, Statistics in Medicine, September 2012 at http://www.ncbi.nlm.nih.gov/pubmed/22961924

Pesticide exposure normally means dioxin exposure: Pesticides have been found to normally contain dioxins, sometimes in high concentrations, even well after major governmental efforts to remove those toxins from pesticides. As of the writing-up of an Australian study published in 2010, many governments were taking new actions to minimize dioxins in pesticides. The study analyzed 27 different formulations of pesticides, including some commonly used products, and found dioxins in all 27. <<The University of Queensland, UQ News: Urgent action needed on dioxins, says toxicologist at https://www.uq.edu.au/news/article/2010/12/urgent-action-needed-dioxins-says-toxicologist

-- Also Holt et al., Polychlorinated Dibenzo-p-Dioxins and Dibenzofurans (PCDD/Fs) Impurities in Pesticides: A Neglected Source of Contemporary Relevance

Environ. Sci. Technol., 2010, at https://pubs.acs.org/doi/abs/10.1021/es903915k

As pointed out earlier, dioxins have proven to be developmentally and neurologically toxic. Therefore they would be well suited as an ingredient in pesticides, since (according to a European/American team of scientists) many pesticides “target the nervous system of insect pests;” that is relevant here because of what the authors call the “similarity of neurochemical processes” between insects and humans. <<Bjorling-Poulsen et al., Potential developmental neurotoxicity of pesticides used in Europe, Environ Health. 2008; 7: 50. PMCID: PMC2577708 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2577708/ If pesticides that producers choose to market essentially always contain dioxins (as found in 27 out of 27 tested in Australia), there is a strong likelihood that the neurological toxicity of the dioxins present in the pesticides is the reason why those formulations were sufficiently effective to be chosen. Remember from earlier that toxicity of dioxin has been observed in humans in association with a body burden even lower than one part per trillion;.<<White and Birnbaum, An Overview of the Effects of Dioxins and Dioxin-like Compounds on Vertebrates, as Documented in Human and Ecological Epidemiology, J Environ Sci Health C Environ Carcinog Ecotoxicol Rev, 2000, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2788749/

-- Also earlier ref so even the small amounts of dioxin ingested along with pesticide residues could be having harmful effects on the cerebellum

Toxicity of dioxins to the nervous system may well be the chief reason why autism has been found to be six times as high close to a pesticide-application area as farther away. Remember from Section 2.a the links that have been found between dioxin exposures and autism.

Section 3: PCBs and dioxins have greater effects on males than on females, specifically in the cerebellum, making a good fit with the uneven sex ratio in autism.

A 2005 experiment investigated neurological development in newborn rats exposed to PCBs during development (gestational day 11 until postnatal day 21), compared with controls. The researchers used PCBs at a dosage.that was compatible with levels found in Belgian children and in a study in the U.S. Performance was impaired in the PCB-exposed putps in four different behavioral tests, with more severe effects on males than on females. Also, cerebellar mass was reduced by the PCB exposure, an effect that was significant even when the overall effect on body mass was figured in, and the effect was greater in males than in females. Summarizing considerable other research on developmental effects of PCB exposures, the authors stated that the other research and their own findings suggest that "changes in cerebellar mass, cerebellar protein expression, and behavior are sex-specific, with a greater effect observed in males."

< Nguon et al., Perinatal exposure to polychlorinated biphenyls differentially affects cerebellar development and motor functions in male and female rat neonates, The Cerebellum, 2005, at https://link.springer.com/article/10.1080/1473422051000780

A study of effects of dioxins on human children arrived at a similar conclusion of greater effects on boys than on girls. Dioxin exposures were determined based on concentrations detected in breast milk samples from the mothers. Findings from that study are shown below. Nishijo et al., 2,3,7,8-Tetrachlorodibenzo-p-dioxin in breast milk increases autistic traits of 3-year-old children in Vietnam, Mol Psychiatry, 2014, at https://www.ncbi.nlm.nih.gov/pubmed/24637425

Notice the greater increase in ASRS (Autism Spectrum Rating Scale) scores among boys than among girls, with similar exposures to dioxin.

The children whose effects from dioxins are shown in the above chart were from a cohort in which all infants were breastfed until four months of age. << Nishijo et al., Impact of Perinatal Dioxin Exposure on Infant Growth: A Cross-Sectional and Longitudinal Studies in Dioxin-Contaminated Areas in Vietnam, PLoS, 2012, at https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0040273

Although the apparent effects of the higher dioxin doses as shown above were statistically significant (especially so in relation to the DSM autism scores), the differences would probably be far greater if data were shown for children whose dioxin exposures continued for two or three times as long, compared with the average, which could well occur.

Very similar results, showing significant adverse neurodevelopmental effects of dioxin exposures on Vietnamese boys but not girls, followed up at age 5 in this case, were found in another study. <<Tran et al., Impacts of Perinatal Dioxin Exposure on Motor Coordination and Higher Cognitive Development in Vietnamese Preschool Children: A Five-Year Follow-Up, PLoS One, 2016, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4732982/

Relevant information is available from a 2009 study by seven Italian researchers (Colciago et al.¹¹) that investigated effects of developmental exposure of rats to PCBs. The doses administered did not cause general toxicity in the animals. After the rats reached adult age, a test of learning ability was conducted with four groups: males and females that had been developmentally exposed to PCBs, and males and females that had not been exposed (control groups). In the first step of that test, the rats stepped into a dark compartment and received a mild shock.

A day later, when again near the entrance to a dark compartment, how well those rats had learned from their previous experiences was indicated by how long they hesitated before entering such a compartment again. In the chart on the right, the results from the four groups are shown in four pairs of bars. There had been only brief delays before first entering, as shown in the left-hand bars in each pair. The lengths of hesitations before entering a dark room on the next day are shown in the right-hand bars; those next-day delays clearly varied considerably according to sex and exposure. As can be seen here, both of the groups that were unexposed to PCBs (controls) had learned from the previous day’s experience to be very cautious; and the exposed females also remembered well enough to be very cautious; but only the males that had been developmentally exposed to PCBs failed to remember their experiences of the day before.

PCBs and dioxins are not the only toxins to have greater effects on males than on females, but these chemicals are apparently outstandingly potent in their greater effects on males than on females. This is highly relevant when discussing origins of a disorder such as ASD that affects males more than females in a very high ratio.

Also, recent data indicates that the disproportionate effect of ASD on males has been becoming even greater in recent years, making this an especially important characteristic to consider when investigating risk factors. See below.

See Appendix C for more research that provides evidence of autism-related effects of these toxins, with greater effects on males than on females

Section 4: The period of greatest sensitivity (especially of the cerebellum), to effects of toxins is the first year after birth.

It is important to focus on the stage of development during which vulnerability to harm by toxins is greatest, since that provides an important clue as to which of various toxins in the environment could be having the most serious effects. Remember from the statement by McCarthy and Wright in Section 1 that "Damage to the cerebellum in infancy is among the highest risk factors for developing ASD (estimated 40 fold increase)." Information to follow will explain why infancy is an especially vulnerable period for the cerebellum, with implications about how harmful exposures could be reduced.

Experts on brain development (Rice and Barone), whose writings are still cited in scientific studies well over a decade later, said that "if exposure (to a toxin) occurs during development" of an organ, it will have more effect than exposure before or after development; they also stated that studies "have clearly demonstrated that when proliferation is actively occurring in a given region of the brain it is vulnerable" to effects of toxins. Rice and Barone, Critical Periods of Vulnerability for the Developing Nervous System: Evidence from Humans and Animal Models, Environmental Health Perspectives * Vol 108, Supplement 3 * June 2000, at https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC1637807&blobtype=pdf

In a publication of the National Academies Press, the authors state that “toxic exposures at a particular time would differentially affect the structures undergoing peak development.” (p. 60)Pesticides in the Diets of Infants and Children, p. 60, Commission on Life Sciences, National Research Council, National Academy Press, Washington, D.C. 1993, at http://www.nap.edu/openbook.php?record_id=2126 “Toxic exposures at a particular time would differentially affect the structures undergoing peak development.”

A publication of WHO states that “developing organs are particularly susceptible to toxic insult, given the increased rate of cell division and immaturity….” WHO: Principles for Evaluating Health Risks in Children Associated with Exposure to Chemicals, Environmental Health Criteria 237, at http://www.inchem.org/documents/ehc/ehc/ehc237.pdf

According to a 2014 study, "Recent studies indicated that low-dose exposure to environmental agents, such as dioxin and PCBs during the period of rapid brain growth, known as the 'brain growth spurt' in neonatal mice can lead to disruption of the adult brain function... "< Nishijo et al., 2,3,7,8-Tetrachlorodibenzo-p-dioxin in breast milk increases autistic traits of 3-year-old children in Vietnam, Mol Psychiatry, 2014, at https://www.ncbi.nlm.nih.gov/pubmed/24637425

-- Also Kim and Yang, Neurotoxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in

cerebellar granule cells, Experimental and Molecular Medicine, Vol. 37, 2005, at https://www.nature.com/articles/emm20058.pdf?origin=ppub

.......................................................................................................................................

<<(4b) 4b) Center on the Developing Child at Harvard University, National Scientific Council on the Developing Child: Early Exposure to Toxic Substances Damages Brain Architecture, 2006, Working Paper No. 4; especially introduction, pp. 2, 7, 9; p. 2: "the time of greatest brain growth and most intensive construction of brain architecture is also the period that is most vulnerable to the relatively free passage of toxins into its cells." Link for this publication at http://developingchild.harvard.edu/resources/early-exposure-to-toxic-substances-damages-brain-architecture/ This Council is comprised of twelve leading scholars from all over the U.S.

In the charts above and below, observe evidence of the above recognized characteristics of periods of greatest vulnerability of the brain to toxins, all being conspicuous during the year after birth: immaturity, rapid growth, and peaks of development.

Also in the chart on the right, observe the growth of the cerebellum during the first year after birth, showing (in a different way) peak development of the cerebellum, the recognized time of greatest vulnerability to toxins. Other research teams verify that most neurons in the cerebellum are created during the year after birth. 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

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

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/

In addition, it is generally recognized that the blood brain barrier is not completed until six months after birth, making the first half-year a time of especially great vulnerability to environmental toxins.

But, even though the blood barrier is normally completed after the first six months, that doesn't mean that the developing brain is not still vulnerable to toxins after that. It has been found in a laboratory experiment that exposure to PCBs reduces the integrity of the blood brain barrier. Seelbach et al., Polychlorinated Biphenyls Disrupt Blood–Brain Barrier Integrity and Promote Brain Metastasis Formation, Environ Health Perspect. 2010 Apr; 118(4): 479–484. Published online 2009 Oct 28. At https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854723/

That could help explain why neurological disorders can develop later in childhood, as a result of initial damage resulting from PCB exposures during infancy; as the child grows older, he is exposed to environmental toxins that he would not have been exposed to in the more sheltered earlier years, being vulnerable at the later age because of damage resulting from exposures during infancy that may have had no apparent effects at the younger age.

As shown below also, most of the sensitive period for the development of the cerebellum in humans is during the first year after birth.

Bearing the above in mind, it is relevant to look back at studies discussed earlier, dealing with the stage at which development was found to go wrong. In the studies of effects of pesticide exposures (in Section 2.b), the time of peak correlation of pesticide exposure with autism incidence (6-fold increase) was found to be in the year after birth.

The chart below shows the developmental periods for which various studies gathered traffic-pollution data, to find associations between pollution exposure and autism. Notice that, for the "Mixed Traffic" category, there was only one study in which the measurements were taken during the year after birth.

Then note that, in that sole study dealing with mixed traffic pollution exposures after birth, the odds ratio for association between the pollution and autism was dramatically higher than the odds found in any of the studies focusing on prenatal exposures.

A final note on the subject of especially high sensitivity to toxins after birth: Note in Figure __ above that formation of connections is postnatal in various functions of the brain, functions that are related to autism. Then note that

-- a 2017 study in the journal, Nature, found that brains of children with ASD have reduced connectivity Zeng et al., Disrupted Brain Network in Children with Autism Spectrum Disorder, Nature, 2017, at https://www.nature.com/articles/s41598-017-16440- z

-- A 2015 study cited 13 studies in support of its statement that "the evidence gathered with recent developments in neuroimaging methods suggests that aberrant brain connectivity reflects important aspects of brain dysfunction in ASD." Kikuchi et al., Reduced long-range functional connectivity in young children with autism spectrum disorder, Social Cognitive and Affective Neuroscience, 2015, at https://academic.oup.com/scan/article/10/2/248/1655738 Those authors also found in their own study "credible evidence indicating that there is reduced connectivity" in the brains of children with ASD, and that "this reduced connectivity was significantly correlated with higher symptom severity."

-- According to the director of the NIH's National Institute of Mental Health (Thomas Insel), "Previous studies have suggested that autism is a developmental disorder resulting from abnormal connections in the brain." National Institutes of Health, News Release: Risk of Autism Tied to Genes that Influence Brain Cell Connections, April 28, 2009, at https://www.nih.gov/news-events/news-releases/risk-autism-tied-genes-influence-brain-cell-connections

To sum up the above: Reduced and/or abnormal connectivity is closely linked with autism, and formation of important connections takes place after birth. That should be considered together with awareness that, according to excellent authority, exposures to PCBs adversely affect neuronal connectivity. Schug et al., Elucidating the Links Between Endocrine Disruptors and Neurodevelopment | Endocrinology June 2015, Vol. 156,

at https://academic.oup.com/endo/article-lookup/doi/10.1210/en.2014-1734

Section 5: In addition to being the period of greatest sensitivity to toxins (especially for the cerebellum), the first year after birth is also the period of greatest exposure to PCBs and dioxins.

On right: Estimated PCB exposures of infants during the first year after birth:

Exposures to PCBs during this period is very much affected by infant feeding type, as well as by duration of any breastfeeding.

The U.S. ATSDR states that "the amount of PCBs transferred to offspring is expected to be higher during lactation than during gestation;" in support of that, the Agency refers to a laboratory experiment as an example: "In female rats administered PCBs before gestation, an average of 0.003% of the administered dose was transferred to the fetus, whereas 5% was transferred to sucklings." U.S. ATSDR, Persistent chemicals found in breast milk, Appendix A, p. 180, at https://www.atsdr.cdc.gov/interactionprofiles/ip-breastmilk/ip03-a.pdf That works out to lactational transfer of PCBs over 1600 times greater than gestational transfer, resulting from the same original prenatal exposure; this is a ratio that the ATSDR obviously considers to be relevant to how human lactational exposure compares with human gestational exposure to those toxins. Studies of humans have found ratios of lactational to gestational transfers of PCBs to be compatible with the above ratio, but with the total transfers obviously being quite variable according to duration of breastfeeding. (See Appendix E.)

Below: Typically high dioxin exposures in infants during a very vulnerable stage of neurological development:

As seen in the chart on the left (similar to the PCBs chart but on a greatly compressed time scale), the pattern of dioxin levels during the sensitive first year after birth is similar to that of PCB levels, with many infants being highly exposed during that stage of development.

U.S. studies from 2002 and 2007 show very much the same pattern as this Australian study but with details for alternative exposure periods, showing progressively smaller increases in dioxin concentrations for longer durations of breastfeeding. (See Appendix F.)

In the case of either PCBs or dioxins, the period of greatest exposure to the chemical is, by far, during the early postnatal period. Bear in mind that these outstanding exposures occur at the stage when the cerebellum, damage to which is closely related to autism, is at its most vulnerable to toxins. (Section 4)

High levels of PCBs continuing into childhood in many children: Although the first year after birth includes the largest amount of vulnerable brain development, there is clearly significant additional neurological development that is vulnerable to toxins in later years as well (see Figure___) Relevant to that, PCB levels have been determined to be high in many children well into the childhood years, as determined in a 1997 study in which PCB levels were actually measured at age 3.5 rather than merely estimated.:

It appears that levels of PCBs in many children continue for several years to be well above the levels at birth, at least as determined in this 1997 Dutch study.

High levels of dioxins, also, can continue well past infancy in breastfed children, as determined in a study by a senior scientist with the EPA Lorber et al., Infant Exposure to Dioxin-like Compounds in Breast Milk, Vol. 110 No. 6, June 2002, Environmental Health Perspectives, Figure 3, at http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=54708#Download,, and as measured in breastfed young men in whom dioxin levels were measured at ages 18 to 26 < 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. at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3094426/

Still-elevated levels of PCBs in these older years is relevant to autism risk especially because of the continuing vulnerability of development of the caudate section of the brain in those years, as will be explained:

-- (a) A Chinese study found that the caudate grew 12% during a 2-year period after age 2 to 3 among controls, but grew an abnormal 17% among ASD cases; < Qiu et al., Two years changes in the development of caudate nucleus are involved in restricted repetitive behaviors in 2–5-year-old children with autism spectrum disorder Developmental Cognitive Neuroscience, Vol. 19, June 2016, Pages 137-143 at https://www.sciencedirect.com/science/article/pii/S187892931530013X that is a strong indication that the caudate is actively developing during those years, and is therefore sensitive to effects of toxins at that time; it also implies that something related to autism could be developing abnormally in the caudate among ASD-affected children during the third and fourth years after birth..

-- (b) Several studies have found enlargement of the caudate nucleus among those with ASD and in addition have specifically found presence of repetitive and/or restricted behaviors (a core trait of ASD) among children with an enlarged caudate nucleus. Langen et al., Changes in the development of striatum are involved in repetitive behavior in autism, Biol Psychiatry, 2014 Sep at https://www.ncbi.nlm.nih.gov/pubmed/24090791

~~37)~~ Sears et al., An MRI study of the basal ganglia in autism, Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 23, Issue 4,

May 1999, at https://www.sciencedirect.com/science/article/pii/S0278584699000202?via%3Dihub

~~38)~~ Langen et al., Changes in the developmental trajectories of striatum in autism, Biol Psychiatry, 2009 Aug at https://www.ncbi.nlm.nih.gov/pubmed/19423078

~~39)~~ Hollander et al., Striatal volume on magnetic resonance imaging and repetitive behaviors in autism, Biol Psychiatry, 2005 Aug 1;58(3):226-32. at https://www.ncbi.nlm.nih.gov/pubmed/15939406 One of those studies also found that increased caudate overgrowth correlated positively with greater repetitive behaviors.³⁹

All of the above implies that levels of PCBs and dioxins that continue to be high for years after birth in many children could be having their (recognized) neurologically toxic effects on the ongoing development of an autism-related brain region.

......................................

Section 6: The predominant source of exposure of the brain to PCBs and dioxins, at highly vulnerable stages of development:

It was pointed out earlier that PCBs and dioxins started to become widespread in the environment in the mid-20th century, before autism became a substantial problem. That was speaking in very general terms, and a closer look at time relationships is justified at this point. More precisely, increases in those toxins in the environment started becoming very significant in the late 1940's and early 1950's (Section 2), and increases in autism appeared to begin in the middle and late 1970's. (See below.)

Above from MF Blaxill, What’s Going On? The Question of Time Trends in Autism, Public Health Reports, 2004, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1497666/pdf/15504445.pdf

There was a gap of about two decades during which the increases of PCBs and dioxins in the environment seemed to be having few if any observed adverse effects. So it is of relevance to look closely at the actual exposures of infants to these toxins, which can be quite different from the presence of the toxins in the environment.

Specifics about how developing infants are heavily exposed to PCBs and dioxins:

PCBs and dioxins (both of which are capable of harming the developing brain -- see here in Section 2.a) are substantially ingested by infants by way of breastfeeding; close look at the charts and text in Section 5 (just above) should make it apparent that that type of feeding is a source of high levels of those toxins in young children. And that would also normally be the only source of high levels of those toxins in young children -- the EPA points out that over 90% of human exposures to both PCBs and dioxins is by way of food consumed; the below-10% from non-food sources could not ordinarily contain PCBs and dioxins in the same order of magnitude as the food source of those toxins indicated in those charts.

Exposures of many infants to PCBs and dioxins in relation to established safe levels:

-- PCBs have been found to be present in human milk in doses 63 to 270 times the minimal risk level established by the U.S. Agency for Toxic Substances and Disease Registry.

Oregon Department of Environmental Quality Environmental Cleanup Program, Oct. 2010, 10-LQ-023, p. D2-4 (attachment 2 of Appendix D, near very end) at

www.oregon.gov/deq/FilterDocs/HumanHealthRiskAssessmentGuidance.pdf A 2013 publication of the UN Environment Programme includes information that is compatible with the figures just above, and also provides additional support for the statement about dioxin levels just below. UNEP: Results of the global survey on concentrations in human milk of persistent organic pollutants by the United Nations Environment Programme and the World Health Organization, Geneva, 2013, at http://www.pops.int/TheConvention/ConferenceoftheParties/Meetings/COP6/tabid/3074/ctl/Download/mid/9701/Default.aspx?id=86&ObjID=16191. See p. 19 in that document. Dioxins have been found to be present in human milk in concentrations exceeding the EPA’s RfD (reference dose, or estimated reasonably safe dose), as well as the U.S. ATSDR's minimum risk level, by scores to hundreds of times. 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)

-- The U.S. ATSDR's minimum risk level (MRL) for semichronic exposure is 1 pg TCDD/kg bw per day <UNEP: Results of the global survey on concentrations in human milk of persistent organic pollutants by the United Nations Environment Programme and the World Health Organization, Geneva, 2013, at http://www.pops.int/TheConvention/ConferenceoftheParties/Meetings/COP6/tabid/3074/ctl/Download/mid/9701/Default.aspx?id=86&ObjID=16191 , p. 19.

Re: breastfed infants’ exposures to dioxins, in U.S. and internationally:

- Arisawa et al., Background exposure to PCDDs/PCDFs/PCBs and its potential health effects : a review of epidemiologic studies, The Journal of Medical Investigation Vol. 52 2005, at https://www.jstage.jst.go.jp/article/jmi/52/1%2C2/52_1%2C2_10/_pdf

- 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.

- Wittsiepe J, PCDD/F and dioxin-like PCB in human blood and milk from German mothers. Chemosphere. 2007 Apr;67(9):S286-94. Epub 2007 Jan 10. www.ncbi.nlm.nih.gov/pubmed/17217986

- 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

According to a major document of the American Academy of Pediatrics published in 2012, referring specifically to PCBs and pesticides, "Infant formula is free of these residues...." (then going on to explain how that result comes about). American Academy of Pediatrics: Pediatric Environmental Health, 3rd Edition, 2012, p. 200.

According to the American Academy of Family Physicians, "throughout the mid-20th century, most physicians did not advocate breastfeeding, and most (American) women did not choose to breastfeed." AAFP: Breastfeeding, Family Physicians Supporting (Position Paper) -- at http://www.aafp.org/about/policies/all/breastfeeding-support.html. So, even though PCBs and dioxins were greatly increasing in the environment during the mid-20th century, the pathway by which infants are exposed to high levels of those toxins (Section 5 ) during sensitive periods of postnatal brain development (Section 4) was relatively inactive during the mid-century decades.

But that changed during the early 1970's. In historical data provided by former U.S. Surgeon General Regina Benjamin, only 5% of U.S. mothers breastfed for six months as of 1971, the first data point shown at the low end of a long-term increase; 20% breastfed for 6 months in 1995, and rates continued increasing in subsequent years. Figure 1 of The Surgeon General’s Call to Action to Support Breastfeeding 2011, p. 33, at www.surgeongeneral.gov/library/calls/breastfeeding/calltoactiontosupportbreastfeeding.pdf Rates of exclusive breastfeeding in the U.S. weren't even indicated in the Surgeon General's data for the years before 2003; it should be safe to say that exclusive breastfeeding was practiced only rarely in the early 1970s, before rising to 10% for 6 months of such feeding in 2005 and much higher later. <CDC web page at https://www.cdc.gov/breastfeeding/data/reportcard.htm

So the major pathway for exposing infants to PCBs and dioxins was very inactive for many years following the increases of those toxins in the U.S. environment, until the early 1970's, which seems to be a reasonable explanation for the lag before effects of the toxins began to be observed.

Regarding the above, it is worth a second look at the Lung et al. study of effects of family proximity to incinerators, which was briefly described earlier. Very minimal effects of the incinerator pollution were found in children in the general population within the designated distance from the incinerator, and effects were found in only one of the areas inquired about; but among children who had been breastfed for at least six months, adverse effects associated with the local incinerator were reported in all four developmental areas that were asked about. Also, the statistical significances were far greater in breastfed children in all four cases. As stated in the Supplemental Material of the Lung et al. study above, the adverse associations in breastfed children were found with p values of 0.003, 0.011, and <0.001 (four at <0.001); all of these were much lower (less likely to result from chance) than the p value of .017 for the one area in which there was significant effect of local incineration on children in the general population. And all four of the areas in which breastfed children were seen to have had worse development were areas that are traits of autism, as follows:

-- deficits in social development and communication are core characteristics of ASD,

-- language impairment is a very common trait of those with ASD, and

-- clumsiness is a common trait of those with ASD; See list of symptoms of ASD at http://www.autismkey.com/autism-symptoms/ consider this in relation to the study's findings of associations of breastfeeding with adverse effects on both gross motor development and fine motor development, as found at various times of measurement in this study.

Several studies have found breastfeeding to be associated with autism diagnoses per se, not merely with autistic traits; and autism has been found to be more prevalent in association with greater duration of breastfeeding:

A 2011 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." Shamberger, R.J., Autism rates associated with nutrition and the WIC program, J Am Coll Nutr. 2011 Oct;30(5):348-53. Abstract at www.ncbi.nlm.nih.gov/pubmed/22081621 An image of part of the article is shown below, since it may be expensive for many readers to see the complete study. Also screenshot from Shamb study.

Note that, according to the EPA, “Epidemiologic studies of exposed human populations provide the most convincing evidence of human health effects.” EPA, The Effects of Great Lakes Contaminants on Human Health, Report to Congress, Section III, p. 12 (bottom) and again on p. 16, at http://nepis.epa.gov/Exe/ZyNET.exe/2000BSHI.txt?ZyActionD=ZyDocument&Client=EPA&Index=1995%20Thru%201999&Docs=&Query=&Time=&EndTime=&SearchMethod=1&TocRestrict=n&Toc=&TocEntry=&QField=&QFieldYear=&QFieldMonth=&QFieldDay=&UseQField=&IntQFieldOp=0&ExtQFieldOp=0&XmlQuery=&File=D%3A%5CZYFILES%5CINDEX%20DATA%5C95THRU99%5CTXT%5C00000002%5C2000BSHI.txt&User=ANONYMOUS&Password=anonymous&SortMethod=h%7C-&MaximumDocuments=1&FuzzyDegree=0&ImageQuality=r75g8/r75g8/x150y150g16/i425&Display=p%7Cf&DefSeekPage=x&SearchBack=ZyActionL&Back=ZyActionS&BackDesc=Results%20page&MaximumPages=10&ZyEntry=20Also, 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, as found in an epidemiological study by a well-published scientist (R.J. Shamberger), was quoted in the previous paragraph. 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 breastfeeding and autism was provided by three other relatively recent studies, with a dose-response relationship being apparent in the overall view of those three studies, with increasing odds of autism in parallel with greater durations of breastfeeding.

-- In a 2011 Canadian study of a population of over 125,000 (Dodds et al.), using discharge from the hospital as the dividing line for breastfeeding exposure, there was a 20% higher autism rate among the breastfed children than among non-breastfed children. Dodds et al., The Role of Prenatal, Obstetric and Neonatal Factors in the Development of Autism, J Autism Dev Disord (July 2011) 41:891–902 DOI 10.1007/s10803-010-1114-8, Table 6, at http://link.springer.com/article/10.1007/s10803-010-1114-8?no-access=true (This article is available only by subscription or $40 payment, so the reader may be satisfied to see the chart provided below, taken from the article.) 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 20 - 25% increased risk of autism among children who were breastfed at discharge from the hospital.

Observe in the chart below that

a) significantly increased odds of autism were found in relation to breastfeeding as determined by three different ways of analyzing the data (from different tables, as brought together below), and

b) the odds of autism in relation to breastfeeding increased with each improvement in the analysis, starting with basic data, then advancing to include consideration of other variables that could affect the outcome, and finally refining the data in a way that makes it most relevant to the great majority of the population (those with low genetic susceptibility).

^{ALSO insert Dodds screenshot}

-- In a 2009 U.K. study, the duration of breastfeeding that was assessed was four weeks versus less than four weeks. 65% of the autism cases had received exclusive breastfeeding for at least four weeks; that should be compared with only about 28% of the general U.K. infant population receiving that much breastfeeding. That meant a 130% higher odds of having had at least four weeks of breastfeeding, among those with autism.

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 https://www.academia.edu/17814363/Trends_in_Developmental_Behavioral_and_somatic_Factors_by_Diagnostic_sub-group_in_pervasive_Developmental_Disorders_A_Follow-up_Analysis. This study found that 65% of autism cases had been exclusively breastfed for at least four weeks; 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, Figure 2.13, at http://www.hscic.gov.uk/catalogue/PUB08694/ifs-uk-2010-chap2-inc-prev-dur.pdf

-- In a 2010 American study in Kentucky by an MD/PhD pair of researchers, the duration of breastfeeding used for comparison was six months. 37% of autism cases had received that much breastfeeding, compared with 13% of the controls, indicating an approximately 185% greater (37%/13%) likelihood that the autism cases would have had that much breastfeeding. The p-value was .003, implying three chances out of a thousand that the finding was a result of chance occurrence. Breastfeeding and Autism P. G. Williams, MD, Pediatrics, University of Louisville, and L. L. Sears, PhD, presented at International Meeting for Autism Research, May 22, 2010, Philadelphia Marriot https://imfar.confex.com/imfr/2010/webprogram/Paper6362.html) This study found a 37% rate of breastfeeding at six months among children diagnosed with autism, as compared with 13% in the control group.

In the Dodds study, significantly increased odds of autism were found in relation to breastfeeding as determined by three different ways of analyzing the data, and the odds of autism in relation to breastfeeding increased with each improvement in the analysis. <<same ref as earlier>>

..............................

47% greater risk of ASD among breastfed children, in another U.S. study:

Other relevant risk information was found in a 2015 study that drew its data from the Autism Genetic Resource Exchange (AGRE). The author reported, based on data from 902 ASD cases and 296 controls, that "maternal self-report of lactation practice (lactation without bottle use) was associated with increased risk of ASD diagnosis.... OR (Odds Ratio) = 1.47, 95% [1.05 - 2.08]." P. 253 of Sullivan, Temporality of Risk Factors and the Gender Differential Related to Autism Spectrum Disorder Diagnosis (PhD thesis), Walden University Scholar Works, 2015, at http://scholarworks.waldenu.edu/cgi/viewcontent.cgi?article=1274&context=dissertations That is, there was a statistically-significant 47% increase in risk of autism associated with breastfeeding. Both "any lactation duration" and "dedicated lactation practice" were associated significantly (p < 0.05) with ASD risk. (p. 230)

Increased risk of autism was associated with greater duration of breastfeeding, and even greater risk of autism was associated with exclusive compared with non-exclusive breastfeeding:

In a 2015 U.S. study (Husk et al.Husk et al., Breastfeeding and Autism Spectrum Disorder in the National Survey of Children's Health, Epidemiology. 2015 Jul;26(4):451-7. Table 3 and accompanying text. Abstract at http://www.ncbi.nlm.nih.gov/pubmed/25872161

), the authors found an increased-odds figure of 1.03 for current autism diagnosis for each additional month of "any" breastfeeding. For exclusive breastfeeding, the adjusted odds ratio was greater than the ratio for any breastfeeding (implying a dose-response relationship), at 1.04 for each additional month of exclusive breastfeeding.

Broadening the range of the data that they analyzed to include children ever diagnosed with ASD, the authors arrived at an adjusted odds ratio of 1.3 (30% increased odds of autism) associated with six months of exclusive breastfeeding versus no breastfeeding. < P. 454, bottom left, of Husk et al. (see above)>

Percentages of children with developmental delays who were breastfed or not breastfed:

First note that children with "developmental delay" very often have traits that overlap considerably with traits of ASD. See CDC document at https://www.cdc.gov/ncbddd/autism/documents/ga-seed-newsletter-13-508.pdf A small study in the U.S. Great Lakes area (Lynch et al., 2012 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.sciencedirect.com/science/article/pii/S0890623812000755

) was the source of the data that follows. A close look at Table 1 of the study indicates that

-- Of the 33 children who were breastfed,* 9 had mental delay, and

-- 100% of the children with mental delay had been breastfed.**

_____________________________________________

* 68.6% of the 35 non-delayed (=24) + all 9 of the delayed children = 33

**as shown in second column of Table 1

The mothers were participants in the New York State Angler Cohort Study, a high-fish-eating group, so their body burdens of PCBs and mercury would have been expected to be above average.

<< Add appendix re European study re exec functn, and Seveso? and pro-bf studies?

European high-bf countries -- Nor, Sw, Hung>>

Section 7: What can be done to minimize the effects of PCBs and dioxins, or to minimize exposures of developing children to those toxins?

Seeing that breastfeeding is such a major source to infants of toxins (Section 5), toxins that could lead to autism-related neurodevelopmental harm (Sections 1 and 2), toxins whose known effects align well with the very uneven male-female ratio of autism prevalence (Section 3), and which are received by infants during a period of high developmental vulnerability (Section 4), one possibility that would occur to some people would be to feed infants with foods other than human milk. That should be especially true considering the extensive associations of breastfeeding with autism diagnoses, as found in published scientific studies (Section 6). But not breastfeeding is an alternative that many people would not consider favorably. Therefore attention should be devoted to

a) urging potential mothers to eat only organic foods, to avoid building up a body burden of dioxins (see Section 2b),

b) keeping potential and current mothers away from vehicular pollution and incineration, to minimize their exposures to PCBs and dioxins (see Section 2.a), and

c) encouraging supplements (vitamin E, at least, and possibly others) that have been found to apparently counter the neuron-damaging effects of toxins in human milk. << >>

For those who are open to rational consideration of scientific evidence, much more will be said below regarding an alternative to breastfeeding.

Lack of rational consideration of infant feeding alternatives, including by the American Academy of Pediatrics:

Although one would expect the association that represents American pediatricians to give well-reasoned consideration to the matter of alternative infant feedings, that turns out not to be the case, at least currently. The author of this article has written to the American Academy of Pediatrics several times requesting responses to valid points concerning the advisability of breastfeeding and has never received a response. Following the original non-responses, subsequent letters included offers of ample financial contributions in order to encourage replies, including offers to place the funds in escrow to assure payment upon receipt of response. The points to which responses were requested (included below) were all reasonable, dealing with matters that any professional organization promoting a specific infant feeding type ought to have responses to, even in the absence of incentives. The AAP's failure to respond to any of the letters that they received (U.S. Postal Service return receipt was requested and received) implies that the AAP is unable to respond in a way that would both defend their position favoring breastfeeding and be supported by adequate evidence.

Following earlier letters (including one offering $2000 for a response) and having received no replies, a letter was sent to the AAP on 8/18/2018 offering $10,000 for a reply; the two points to which the AAP was asked to respond in that letter (with responses to be based on published scientific evidence) were as follows:

1) Essentially all of the studies that have found benefits of breastfeeding have been of the observational type, according to former Surgeon General Regina Benjamin.¹ Leading authorities on medical evidence, including the chief editor of the American Medical Association’s Manual for Evidence-based Clinical Practice, as well as the doctor who is widely considered to have been the father of evidence-based medicine, have stated that evidence from observational studies is very predominantly of low quality.^2,3

1) The Surgeon General’s Call to Action to Support Breastfeeding 2011, p. 33, at www.surgeongeneral.gov/library/calls/breastfeeding/calltoactiontosupportbreastfeeding.pdf The Surgeon General stated, "research on the health outcomes of different modes of infant feeding is limited to observational studies."

2) Figure 2 in Guyatt et al., GRADE guidelines: 1. Introduction -- GRADE evidence profiles and summary of findings tables, Journal of Clinical Epidemiology, at http://www.jclinepi.com/article/S0895-4356(10)00330-6/pdf Dr. Gordon Guyatt is chief editor of Users' Guides to the Medical Literature: A Manual for Evidence-based Clinical Practice, 2^nd Edition, copyright American Medical Association; 26 pages of this manual are devoted to examples of studies (almost all of which were observational) that were later refuted by high-quality studies.

3) Dr. David Sackett, writing in The Canadian Medical Association Journal, as quoted in “Do We Really Know What Makes Us Healthy?” New York Times, published: September 16, 2007 at http://www.nytimes.com/2007/09/16/magazine/16epidemiology-t.html?pagewanted=2&_r=0 Dr. Sackett's reputation: BMJ 2015;350:h2639, at https://www.bmj.com/content/350/bmj.h2639

2) PCBs have been found to be present in human milk in doses 63 to 270 times the minimal risk level established by the U.S. Agency for Toxic Substances and Disease Registry.^4,6 Dioxins have been found to be present in typical U.S. human milk in concentrations exceeding the EPA’s RfD (estimated reasonably safe dose) by scores to hundreds of times.^5,6 PCBs have been found to have long-term effects including cancer^7,9 and damage to the blood-brain barrier. ⁸ Dioxins have been found to have long-term effects including cancer, heart disease, reproductive abnormalities, and immunity deficits.^9,10 Therefore early outcomes following infant exposures have only limited significance.

4) Oregon Department of Environmental Quality Environmental Cleanup Program, Oct. 2010, 10-LQ-023, p. D2-4 (attachment 2 of Appendix D, near very end) at

www.oregon.gov/deq/FilterDocs/HumanHealthRiskAssessmentGuidance.pdf

5) 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. Re: EPA’s RfD for dioxin: See reference 6 below.

6) UNEP: Results of the global survey on concentrations in human milk of persistent organic pollutants by the United Nations Environment Programme and the World Health Organization, Geneva, 2013, at http://www.pops.int/TheConvention/ConferenceoftheParties/Meetings/COP6/tabid/3074/ctl/Download/mid/9701/Default.aspx?id=86&ObjID=16191. See p. 19 in that document.

7) Van den Berg et al., Toxic Equivalency Factors (TEFs) for PCBs, PCDDs, PCDFs for Humans and

Wildlife, Environmental Health Perspectives * Volume 106, Number 12, December 1998, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1533232/pdf/envhper00535-0049.pdf

8) Seelbach et al., Polychlorinated Biphenyls Disrupt Blood–Brain Barrier Integrity and Promote Brain Metastasis Formation, Environ Health Perspect, 2010 Apr; 118(4): 479–484. Published online 2009 Oct 28. At https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854723/

9) Baker et al., Adverse effects in adulthood resulting from low-level dioxin exposure in juvenile zebrafish, Endocrine Disruptors, Volume 2, 2014 - Issue 1 Published online: 05 Mar 2014 at https://www.tandfonline.com/doi/full/10.4161/endo.28309

10) ten Tusscher et al., Findings on prenatal, lactational and later childhood exposure to dioxins and dioxin-like compounds: a review of the Amersterdam-Zaandam cohort 1987-2005, AIMS Environmental Science, Volume 2, Issue 1, 1-20, Feb. 2015, at https://www.researchgate.net/publication/272437172_Findings_on_prenatal_lactational_and_later_childhood_exposure_to_dioxins_and_dioxin-like_compounds_a_review_of_the_Amsterdam-Zaandam_cohort_1987-2005

In the next letter (of 10/5/2018), responses to the other points below were also requested, offering $4000 per item for responses (expected to be based on published evidence):

1). Of toxins with recognized long-term effects, none are known to be ingested or inhaled by U.S. infants in doses beyond established safe levels except for toxins that are transferred via breast milk.

2) According to a major 2012 document of the American Academy of Pediatrics, referring specifically to PCBs, PBDEs, and major types of pesticides, "Infant formula is free of these residues...."¹ Other authoritative evidence indicates extremely little dioxin in infant formula, compared with that in human milk.²

_________________

¹American Academy of Pediatrics: Pediatric Environmental Health, 3rd Edition, 2012, p. 200

² Evidence from studies on this topic can be found in Section 3.c of www.pollution-effects.info/.

3) Obesity, diabetes, asthma, allergies, ADHD, cancer, autism, and other non-communicable disorders have all increased among U.S. children during the years when breastfeeding was greatly increasing in recent decades. The first five of the above disorders increased dramatically during those years.

4) Many published scientific studies, especially epidemiological studies, have found autism prevalence to be associated with rates of breastfeeding; among them was a 2011 study of all 50 U.S. states and 51 U.S. counties that found, "the longer the duration of exclusive breast-feeding, the greater the correlation with autism." Applicable studies can be found in Section 4.a of www.pollution-effects.info

All of the above points are based on publicly-available, published information from authoritative sources. And they all deal with matters that ought to be considered by parents who are deciding about what to feed their infants. If any of those statements were not in accord with high-quality, published scientific evidence, it would be relatively easy for the AAP to write responses in disagreement and thereby (a) collect the financial contributions offered and (b) defend the case they are making in favor of breastfeeding, in reply to contradictory evidence. Their complete lack of response is an indication that their position on breastfeeding is weak. If anybody can think of any reason for their non-response other than that, please e-mail to dm@pollutionaction.org and your explanation will be posted in the comments section of www.pollutionaction.org. Likewise, if anybody sees anything incorrect in the statements just below, please write to tell others how they are inaccurate.

1) On the basis of a type of evidence that highest authorities on medical evidence consider to be of low quality, the AAP strongly recommends that vulnerable, developing infants be fed a substance that includes extremely high levels of recognized developmental toxins. The AAP does not dispute the information included in this statement.

2) While promoting breastfeeding, the AAP withholds from parents undisputed information about the high levels of developmental toxins contained in human milk, and about the many studies that have found harmful effects of breastfeeding. Aside from the several studies that have found breastfeeding and duration of breastfeeding to be associated with autism and higher prevalence of autism (see Section 6), there have been dozens of studies (including the gold-standard type -- randomized controlled trials) that have found other adverse effects of breastfeeding. (See www.breastfeeding-studies.info)

3) Given the conflicting nature and the quality concerns about the evidence regarding advisability of breastfeeding, it makes sense to see what has actually happened during the decades when breastfeeding greatly increased in the U.S. As shown in the chart (below) provided by the U.S. Surgeon General, breastfeeding rates in the U.S. have dramatically increased since the early 1970's.

Other authoritative evidence indicates that breastfeeding actually started increasing, although relatively slowly, in 1965. << Fomon: Infant feeding in the 20th Century: Formula and Beikost, J. Nutr., Feb. 2001, Fig. 5, at http://jn.nutrition.org/content/131/2/409S.full>> But for a useful approximation, 1970 can be considered to be the starting point for major increases of breastfeeding in the U.S.

Notice that breastfeeding for at least 6 months has increased about 10-fold since 1970. The still-longer durations of breastfeeding, which have been promoted and more widely practiced in recent years, are likely to have increased by at least that much since 1970; that is implied by the relationship between longer duration and great relative increase as shown in the trend line for 6 months of breastfeeding.

Obesity is one of the disorders said by the AAP to be reduced by breastfeeding, << AAP Policy Statement on breastfeeding, at http://pediatrics.aappublications.org/content/129/3/e827.full#content-block based on evidence that high authorities on medical evidence say is of low quality, a fact that the AAP does not dispute. So it is relevant to see what actually happened to child obesity in the years since breastfeeding greatly increased in the U.S. See below.

When breastfeeding increased dramatically, child obesity also increased greatly, casting additional doubt on the conclusions of the studies that the American Academy of Pediatrics chooses to quote. The same is true for diabetes and allergies.<<>>

It should be of no surprise that the above report of what actually happened historically aligns well with what was found in a large study of over 17,000 children followed from birth to age 16 (conducted by four PhD's and four MD's), a study that incorporated randomization of breastfeeding promotion; Martin et al., Effects of Promoting Long-term, Exclusive Breastfeeding on Adolescent Adiposity, Blood Pressure, and Growth Trajectories: A Secondary Analysis of a Randomized Clinical Trial, JAMA Pediatrics, at https://jamanetwork.com/journals/jamapediatrics/fullarticle/2624341

randomization helps avoid the confounding that is inevitably present in observational studies, the kind that the AAP cites in support of its promotion of breastfeeding. Observational studies find associations, such as would be found between high death rates in Florida and sunshine. Researchers typically feel that they can identify and properly deal with confounders (underlying actual causes, such as the large elderly population in Florida), but they can't do that well, according to experts on medical evidence. O'Neil and 7 others, Observational evidence and strength of evidence domains: case examples, Biomed Central: Systematic Reviews, at https://systematicreviewsjournal.biomedcentral.com/articles/10.1186/2046-4053-3-35

Gary Taubes, Do We Really Know What Makes Us Healthy? The New York Times Magazine, Sept. 16, 2007, at http://www.nytimes.com/2007/09/16/magazine/16epidemiology-t.html?_r=0

Also see references in letter to AAP

Also see Section 10 of www.pollution-effects.info

According to the president of the American Diabetes Association, as of 2002 type 2 diabetes had "changed from a disease of our grandparents and parents to a disease of our children." At that time it was on its way to being what she called a "new epidemic" among children and young adults. 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 Also, a Univ. of Michigan article published in 2008 reported, “Recent studies suggest that there have been dramatic increases in type 2 diabetes among individuals in their 20s and 30s...." (at http://www2.med.umich.edu/prmc/media/newsroom/details.cfm?ID=422), which is compatible with origins of the epidemic in infant development after 1972.

^ALSO

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

Also, a Univ. of Michigan article published in 2008 reported, “Recent studies suggest that there have been dramatic increases in type 2 diabetes among individuals in their 20s and 30s...." (at http://www2.med.umich.edu/prmc/media/newsroom/details.cfm?ID=422), which is compatible with origins of the epidemic in infant development after 1972.

According to the only readily-found study on the history of the increase of childhood diabetes, "the rising incidence of the condition was not widely recognized until the 1980s;" American Diabetes Assn., Diabetes, The Rise of Childhood Type 1 Diabetes in the 20th Century, Edwin A.M. Gale, Department of Diabetes and Metabolism, Division of Medicine, University of Bristol, U.K

and the first reference found by this author (after substantial search) to inclusion of young adults within this epidemic was in 2002. All of this points toward the origin of the major increase in childhood diabetes coming some time after the start of the increases in breastfeeding. (For much more on this topic, see www.breastfeeding-and-diabetes.info.)

The AAP, when providing evidence to support its "conclusion that breastfeeding and human milk are the reference normative standards for infant feeding and nutrition," indicates allergic disease as another disease that is decreased by breastfeeding. In relation to that, it is relevant to see what happened to major types of allergies in the 2000's.

Observe in Figure __ earlier that babies born after 1990 would have gone through dramatic increases in exposure to breastfeeding, only partly because of the increases in percentages of breastfeeding; exclusiveness of breastfeeding was apparently first becoming significant in infant feeding somewhere around the turn of the century. ("The concept of exclusive breastfeeding is new...," as stated in a 2008 article in Encyclopedia on Early Childhood Development; in the historical account provided in that article, the first mention of an organization's recommendation of exclusive breastfeeding was in 1997.<<Breastfeeding, by Ted Greiner, at http://www.child-encyclopedia.com/breastfeeding/according-experts/programs-protect-support-and-promote-breastfeeding referring to beginnings of theory of the practice in the last part of the 20th century, leading to a 1997 recommendation of it by WHO.>> The Surgeon General was not able to provide data about exclusive breastfeeding for before 2003.) The newly-significant exclusiveness of breastfeeding probably greatly amplified the effects of breastfeeding exposure, well beyond the simple percentage increases in nursing rates. If breastfeeding were to have an effect of reducing allergic disease, we should certainly expect to see evidence of that in data for the 2000's. But what we instead see (in the chart above) following dramatic increases in breastfeeding is dramatic increases in allergic disease. Notice that very large increases in both food allergy and skin allergy were shown for every one of the individual age groups shown in this chart, without exception; all of those age groups would have been exposed to the greatly increasing breastfeeding of the 1990's and 2000's.

Aside from the various diseases that are alleged by the AAP to be decreased by breastfeeding (in contrast with what actually happened -- see above), also of interest are changes that have occurred in important health areas not discussed by the AAP, during the years when breastfeeding was increasing greatly. Of particular interest are changes in child health data for after 2000, following exposures to breastfeeding that were greatly increasing in intensity as well as numbers; the early 2000's are also the period for which the available health data is most complete.

The chart on the left is fairly self-explanatory, showing what has happened regarding the health of many American children who were infants during the 1990-2010 major increases in breastfeeding. (Increases in breastfeeding continued well after the data shown above in Figure ___ <<CDC news release of 8/22/2016>>

As reported in a study in the journal Pediatrics, by a team that included six doctoral degrees within the group, 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 , Table 2 among U.S. children aged 0-17 there were the following

major increases between 2001 and 2011

-- disability associated with speech problems (63.1%),

-- mental retardation or intellectual impairment (63%), and

-- other mental, emotional, or behavioral problems (64.7%).

For gathering their data, the researchers utilized "the only continuing nationwide survey" of U.S. health information, one that is conducted annually by the CDC's National Center for Health Statistics (NCHS) and which has been the principal source of information for the U.S. Department of Health and Human Services to monitor health trends in the United States since 1957. Note that the above large increases all occurred during just one decade, following large increases in breastfeeding exposures (in exclusiveness as well as percentages) that were high for the children whose health data is shown.

The AAP also discusses neurodevelopmental outcomes as an area showing benefits of breastfeeding. Recent increases in neurodevelopmental impairments, following increases in breastfeeding exposures, were shown just above. That is an area whose longer-term history is also worth a close look, going back to the 1970's when the rapid breastfeeding increases began. A 2008 publication of the U.S. Center for National Health Statistics states as follows: “Over the past three decades in the United States, behavioral and learning disorders have emerged as major chronic conditions affecting the development of school-aged children and adolescents.” (This statement was based on observations of pediatricians and educators as well as government statistics.) Pastor et al., Diagnosed attention deficit hyperactivity disorder and learning disability: United States 2004-2006, National Center for Health Statistics, 2008, at http://www.cdc.gov/nchs/data/series/sr_10/Sr10_237.pdf

A 2012 study by a team of scientists from the U.S., France, U.K., Denmark and New Zealand referred to the “many… major diseases – and dysfunctions – that have increased substantially in prevalence over the last 40 years;” their primary focus, regarding possible causal factors in the environment, was on the period of early development.⁶

Barouki et al., Developmental origins of non-communicable disease: Implications for research and public health, Environ Health. 2012; 11: 42. PMCID: PMC3384466 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3384466/

So it is worth taking a closer look at what has been happening in U.S. health matters beginning in the 1970's, aside from increases in breastfeeding. Dealing with neurological development specifically, the EPA reports (in a 2015 document), "Some researchers have stated that the prevalence of certain neurodevelopmental disorders, specifically autism and ADHD, has been increasing over the last four decades." (citing five studies, and expressing no disagreement with the statements described.) Pp. 233 and 238 of EPA: America's Children and the Environment, at https://www.epa.gov/sites/production/files/2015-06/documents/ace3_2013.pdf

Also ADHD increases,

It would be worth going back up to Figure __ and skimming down to this point, to review all of the major increases in child health problems that have actually occurred during the years when breastfeeding was increasing greatly, while asking oneself the question, "Would all of this have been occurring if breastfeeding actually had beneficial effects overall?" Bear in mind that the AAP does not deny that typical human milk contains both PCBs and dioxins in concentrations scores to hundreds of times higher than established safe levels.

and ASD.

Environmental toxins have been decreasing during these years: lead, traffic pollution, PCBs, dioxins, so shouldn't be causing the impairment increases.

..................................

Given the history of what has actually occurred in health of U.S. children during the decades since breastfeeding rates have increased greatly, should an alternative infant feeding be considered? Remember (from "Lack of rational consideration..." earlier) that the American Academy of Family Physicians does not dispute that

-- essentially all of the studies that have found benefits of breastfeeding have been of the observational type, evidence from which leading authorities on medical evidence consider to be very predominantly of low quality, and

-- typical human milk contains both PCBs and dioxins in concentrations scores to hundreds of times higher than established safe doses, while infant formula has little or none of these as well as no other toxins exceeding established safe levels.

What was wrong with the health of the seldom-breastfed generation that was born in the middle of the 20th century? They did not have the many epidemics and large increases of diseases that have come about since the beginning of the 1970's.

Should parents be informed of the reasons to doubt the advisability of breastfeeding, rather than hearing only strong recommendations from the authority figures to whom they are exposed?

Obviously, other recent sources of toxins in the environment may have been responsible for.. But (picking up from earlier): of toxins with recognized long-term effects, none are known to be ingested or inhaled by U.S. infants in doses beyond established safe levels except for toxins that are transferred via breast milk. Again, the AAP does not dispute this. (quote from lead expert re extensive study of toxins)

Big question: Is low-quality evidence sufficient basis to justify feeding infants a substance that undisputedly contains developmental toxins far exceeding established safe doses, especially considering all the disease increases and epidemics that have arisen among children since breastfeeding began to increase?

Bear in mind that the American Academy of Pediatrics does not dispute the facts on which the above question is based.

Appendix A: More about the relationship between autism and harm to the cerebellum:

In a laboratory experiment, the vermis section of the cerebellum in rats was subjected to damage during development, and the mice were later observed in adulthood, compared with controls; "obvious autistic-like symptoms" observed in the cerebellum-damaged rats led the study's authors to state, "since a number of autistic subjects have cerebellar deficits and, particularly, a hypoplasia of vermal lobules, our results may strengthen the idea that the cerebellar vermis is involved in autism, as already suggested in the guinea pig."

<<Bobee et al., Effects of early midline cerebellar lesion on cognitive and emotional functions in the rat, Behav Brain Res., 2000, at https://www.ncbi.nlm.nih.gov/pubmed/10862941

A study published later (2012), utilizing magnetic resonance scanning with children averaging 29 months of age, found that "In children with cerebellar malformations, decreased total cerebellar volume was associated with delays in global development, expressive language, cognition, as well as gross and fine motor function." Observing the vermis section of the cerebellum separately, they found reduced volume of that section to have all of the above associations with a high level of statistical significance, "as well as behavior problems and a higher rate of positive autism spectrum screening test." The authors expressed surprise at "the apparent pervasive functional impact of disturbed cerebellar vermis growth at this young age." Note the strong statement of cause and effect that the researchers felt was justified when discussing autism-related effects of abnormalities in the cerebellar vermis.)<<Bolduc et al., Regional Cerebellar Volumes Predict Functional Outcome in Children with Cerebellar Malformations, Cerebellum, 2012, Vol. 11, at https://www.ncbi.nlm.nih.gov/pubmed/21901523

The above study was a recent link in a long-ongoing history of research that has implicated the cerebellum in autism, research that was already well underway as of 1991; in that year an article in the journal Pediatrics stated, "one of the most frequently found abnormalities in autism with and without mental retardation is a reduction of cerebellar tissue." (citing 16 studies) <Courchesne, Neuroanatomic imaging in autism, Pediatrics,1991 at https://www.ncbi.nlm.nih.gov/pubmed/2020537>> By 1995, the research was focusing especially on abnormalities found in the vermis section of the cerebellum.

<<Hashimoto et al., Development of the brainstem and cerebellum in autistic patients, J Autism Dev Disord., 1995

A 2009 study looked into correlations between autism and measures of volume of the cerebellum in past studies and found inconsistencies among many of the reports; but the authors found no inconsistencies in the findings (among at least five reports) about decreased volume in specific subsections of the vermis section of the cerebellum in children with autism; their own study arrived at the same type of finding. The authors pointed out that their observation "may be a general anatomical finding associated with ASD, consistent with the results of a meta analysis which noted that between 84%- 92% of individuals with ASD exhibited vermal hypoplasia." <<Webb et al., Cerebellar vermal volumes and behavioral correlates in children with autism spectrum disorder, Psychiatry Res., 2009, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2676721/

A 2017 review of MRI studies summarizes, "The cerebellum is considered to be one of the most consistent sites of abnormality in autism. Most morphometric studies of ASD children have reported increased total cerebellar volume (citing three studies) and decreased GMV in some subregions" (citing another three studies).(italics added) The authors pointed out that there have been inconsistencies in the reports. <Li et al., Candidate Biomarkers in Children with Autism Spectrum Disorder: A Review of MRI Studies, Neurosci Bull., 2017, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360855/ But those inconsistencies seem to be explainable on the basis of differences in what is measured (volume versus density, different sections of the brain), and age of measuring -- there are different influences at different times, such as complete blood brain barrier after 6 months of age versus incomplete before then, and special sensitivity of the cerebellum to toxins during the first year after birth (see Section 2).

Appendix B: More about adverse effects of these toxins on the cerebellum:

In a 2010 study, rat pups were exposed to PCBs in doses higher than typical background levels but three-fold lower than levels found in infants exposed via mothers who had consumed seafood. Cell death (apoptosis) and oxidative damage were measured in three major brain regions after birth and at weaning; the largest effect was observed in the cerebellum. The authors found that brain cell death as well as markers of oxidative damage were significantly increased by the PCB exposure at an early stage of development. The exposures were mild enough that they "did not negatively impact developmental outcomes or cause overt signs of intoxication in dams or pups." <Yang and Lein, Polychlorinated biphenyls increase apoptosis in the developing rat brain, Current Neurobiology, 2010, at http://www.indmedica.com/journals.php?journalid=14&issueid=139&articleid=1843&action=article (cerAut39)

Thyroid hormone is essential for normal brain development, and PCBs are known to interfere with thyroid hormone action in the developing brain;. the cerebellum was found in an animal experiment to be particularly sensitive to thyroid hormone insufficiency during development. << Bansal and Zoeller, Polychlorinated Biphenyls (Aroclor 1254) Do Not Uniformly Produce Agonist Actions on Thyroid Hormone Responses in the Developing Rat Brain, Epidemiology, 2008, at https://academic.oup.com/endo/article/149/8/4001/2455611

Appendix C: GFAP (Glial Fibrillary Acidic Protein), a protein that is important to brain development and health in several areas, is reduced by both PCB and dioxin exposures, in a dose-dependent manner, and in males but not females. Miller et al., Developmental PCB exposure induces hypothyroxinemia and sex-specific effects on cerebellum glial protein levels in rats, Int J Dev Neurosci, 2010, Fig. 5b, at http://europepmc.org/articles/pmc2939295

-- Takanaga et al., Inhibitory effect of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin on cAMP‐induced differentiation of rat C6 glial cell line, Journal of Neuroscience Research, 2001, at https://onlinelibrary.wiley.com/doi/pdf/10.1002/jnr.1091

GFAP is a component of the brain with several important functions: This is illustrated in the figure below from a study by two highly-published experts in the field.

Above from Middeldorp and Hol, GFAP in health and disease, Progress in Neurobiology, 2011, at https://www.sciencedirect.com/science/article/pii/S0301008211000062?via%3Dihub

This was from a 2011 study by two experts in neurology, with impressive credentials and expertise indicated by many directly-related publications (Middeldorp and Hol << -- J. Middeldorp, Stanford University School of Medicine, Department of Astrocyte Biology & Neurodegeneration, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands; author or co-author of 12 publications on neurological impairments, 9 of them with "GFAP" in the titles.

-- E. Hol, also with Department of Astrocyte Biology & Neurodegeneration, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands, is author or co-author or 20 publications on neurology, five of them with "GFAP" in the title. These authors discussed nine "cellular processes in the brain, in which GFAP has been shown to play a role;" several of those processes are indicated in this figure.

Serum levels of GFAP have been found to be significantly lower in ASD cases than in controls in some research, Cetin et al., Serum levels of glial fibrillary acidic protein and Nogo-A in children with autism spectrum disorders, Biomarkers, 2016, at https://www.tandfonline.com/doi/abs/10.3109/1354750X.2016.1171901 but those levels have been found to be higher in ASD cases than in non-ASD children in some other studies. The different findings are very likely a matter of the age at which the GFAP levels are measured. GFAP levels would be reduced when PCB and dioxin levels are high, in very early childhood (see Section 4) But the GFAP levels would rise again in later years when the PCB and dioxin levels decline greatly, and they would rise to above-normal levels in response to nerve cell damage that was present by then, a kind of response that has been found to occur. <<Kern and Jones, Evidence of toxicity, oxidative stress, and neuronal insult in autism, Journal of Toxicology and Environmental Health, Part B, 2006, at https://pdfs.semanticscholar.org/99a4/b3ca5d7f27fc1c3eb4be5c24590293e58f45.pdf

- Triolo et al., Loss of glial fibrillary acidic protein (GFAP) impairs Schwann cell proliferation and delays nerve regeneration after damage, Journal of Cell Science, 2006, at http://jcs.biologists.org/content/119/19/3981>> In any case, both PCBs and dioxins have been found to decrease GFAP, although only in males in the case of PCBs (see previous paragraph).

Above from Miller et al., Developmental PCB exposure induces hypothyroxinemia and sex-specific effects on cerebellum glial protein levels in rats, Int J Dev Neurosci, 2010, at http://europepmc.org/articles/pmc2939295

((discuss lack of effect at PND 42, by which time PCB levels far lower, postweaning))

Appendix D: Burning of plastics as a predominant source of dioxin emissions in the environment:

According to the EPA, current theory proposes that dioxins are formed within the cool-down region of combustion processes, when carbon, oxygen and chlorine (as in polyvinyl chloride, PVC) are all present.^{EPA: An Inventory of
Sources and Environmental Releases of Dioxin-Like Compounds in the United
States for the Years 1987, 1995, and 2000, EPA/600/P-03/002F November 2006,
Table 1-12, at https://cfpub.epa.gov/ncea/dioxin/recordisplay.cfm?deid=159286
; under Downloads, choose to download the Dioxin Inventory of Sources
(Optimized Report).} The EPA reports that backyard barrel burning of trash is a very major source of such dioxin emissions; ^{At the EPA
"An Inventory of Sources...." listed above, see p. xliv and Section
6.5, "Backyard Barrel Burning."} trash (beginning in the mid-20th century) would typically contain PVC plastics as well as coated paper and other chlorine-containing materials. Household and farm burning of trash is common in rural and non-urban U.S.^{At the EPA "An
Inventory of Sources...." listed above, see p. xliv and Section 6.5,
"Backyard Barrel Burning."}

^--^{New York Times: In Rural Areas, the Heat Is
on Over Practice of Trash Burning, By Lisa W. Foderaro, MARCH 7, 2005 , at https://www.nytimes.com/2005/03/07/nyregion/in-rural-areas-the-heat-is-on-over-practice-of-trash-burning.html?pagewanted=all} The EPA considers backyard barrel burning to be the largest quantifiable source of dioxin emissions in the U.S. as of the latest national inventory. EPA: An Inventory of Sources and Environmental Releases of Dioxin-Like Compounds in the United States for the Years 1987, 1995, and 2000, especially Table 1-17 ofmpub.epa.gov/eims/eimscomm.getfile?p_download_id=523391 Compared with combustion in municipal incinerators, open burning typically takes place mainly in the lower end of the temperature range, where dioxins are most readily formed.

Appendix E: Human studies regarding postnatal versus prenatal transfers of PCBs from the mother:

In human studies summarized in a publication of the National Academies Press, the comparisons that were most relevant to the pattern discussed in the main text yielded ratios of about 280 to 1 and 775 to 1;National Academies Press, Hormonally Active Agents in the Environment (1999), Chapter: 6: Neurologic Effects, at http://www.nap.edu/read/6029/chapter/8#178, p. 178. Describing studies measuring maternal concentrations of developmental toxins in 313 women in Michigan, this publication states, “The mean concentrations of PCBs were 6 ng/mL in maternal serum, 3 ng/mL in cord serum, and 841 ng/g in breast milk.”(p. 178) From a German study (Winneke et al., 1998), “Mean concentrations of PCBs were 0.55 ng/mL in cord blood and 427 ng/g in the fat of breast milk.” (p. 183) (1 mL is about the same as 1 g when discussing a substance whose weight is about the same as that of water.) the specific comparisons in those cases were of PCB concentrations in breast milk in relation to PCB contents in umbilical cord serum and cord blood; so the actual total ingestions of PCBs by infants would obviously be determined by how long breastfeeding continued.

Appendix F: More on dioxin levels in young children, from U.S. studies:

This chart is from Kerger et al., An Adaptable Internal Dose Model for Risk Assessment of Dietary and Soil Dioxin Exposures in Young Children, Toxicological Sciences 100(1), 224–237 (2007), at https://academic.oup.com/toxsci/article/100/1/224/1623981

Although this dioxin-levels chart looks different from the charts in the main text, it actually shows very much the same thing about the patterns of postnatal levels of these toxins.

For another U.S. study showing a similar pattern but with measures of accumulated exposures, which are more extended in time, being the focus, see

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,

_____________________

(1) McCarthy and Wright, Convergence of sex differences and the neuroimmune system in Autism Spectrum Disorders, Biol Psychiatry, 2017, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5285451/

(2) Limperopoulos et al., Does cerebellar injury in premature infants contribute to the high prevalence of long-term cognitive, learning, and behavioral disability in survivors?, Pediatrics, 2007, at https://www.ncbi.nlm.nih.gov/pubmed/17766532/

(3) Wang et al., The Cerebellum, Sensitive Periods, and Autism, Neuron, 2014, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135479/

(3a) Enlargement, as well as reduction, of the cerebellum has been linked with ASD: A typical pattern of cellular growth during sensitive periods is initial exuberant growth of cells and connections, followed by pruning of extraneous connections; programmed cell death (apoptosis) is also known to follow initial excess proliferation of cells. Failures of pruning and apoptosis are known to occur as a result of exposures to toxins, and these can be expected to result in volume increases. Three studies have found enlargement of the total cerebellum in autism, although those volumes were proportional to enlarged brain volume. <<Webb et al., Cerebellar vermal volumes and behavioral correlates in children with autism spectrum disorder, Psychiatry Res., 2009, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2676721/>> Other studies have found enlargement of the entire brain in autism, but the reports on this have not been entirely consistent. <<Ismail et al., Studying Autism Spectrum Disorder with Structural and Diffusion Magnetic Resonance Imaging: A Survey, Front Hum Neurol., 2016, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862981/

(4) Allen and Courchesne, Differential effects of developmental cerebellar abnormality on cognitive and motor functions in the cerebellum: an fMRI study of autism, Am J Psychiatry, 2003, at https://www.ncbi.nlm.nih.gov/pubmed/12562572

5) D'Mello et al., Cerebellar gray matter and lobular volumes correlate with core autism symptoms, Neuromiage Clin., 2016, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375648/

......................................

Autism is called a "spectrum" disorder because people with ASD can have a range of symptoms. <<Medline Plus.gov web page at https://medlineplus.gov/autismspectrumdisorder.html

*About the author:

As the author of the above, my role has not been to carry out original research, but instead it has been to read through very large amounts of scientific research that has already been completed on the subjects of environmental toxins and infant development, and then to summarize the relevant findings; my aim has been to put this information into a form that enables readers to make better-informed decisions related to these matters. The original research articles and government reports on this subject (my sources) are extremely numerous, often very lengthy, and are usually written in a form and stored in locations such that the general public is normally unable to learn from them.

My main qualification for writing these publications is ability to find and pull together large amounts of scientific evidence from authoritative sources and to condense the most significant parts into a form that is reasonably understandable to the general public and also sufficiently accurate as to be useful to interested professionals. My educational background included challenging courses in biology and chemistry in which I did very well, but at least as important has been an ability to correctly summarize in plain English large amounts of scientific material. I scored in the top one percent in standardized tests in high school, graduated cum laude from Oberlin College, and stood in the top third of my class at Harvard Business School.

There were important aspects of the business school case-study method that have been helpful in making my work more useful than much or most of what has been written on this subject, as follows: After carefully studying large amounts of printed matter on a subject, one is expected to come up with well-considered recommendations that can be defended against criticisms from all directions. The expected criticisms ingrain the habits of (a) maintaining accuracy in what one says, and (b) not making recommendations unless one can support them with good evidence and logical reasoning. Established policies receive little respect if they can’t be well supported as part of a free give-and-take of conflicting evidence and reasoning. That approach is especially relevant to the position statements on breastfeeding of the American Academy of Pediatrics and the American Academy of Family Physicians, which statements cite only evidence that has been

(a) selected, while in no way acknowledging the considerable contrary evidence,^a1 and

(b) of a kind that has been authoritatively determined to be of low quality. (See "Lack of rational consideration..." in Section 7 above.)

When a brief summary of material that conflicts with their breastfeeding positions is repeatedly presented to the physicians’ associations, along with a question or two about the basis for their breastfeeding recommendations, those associations never respond. That says a great deal about how well their positions on breastfeeding can stand up to scrutiny.

The credibility of the contents of the above article is based on the authoritative sources that are referred to in the references: The sources are mainly U.S. government health-related agencies and reputable academic researchers (typically highly-published authors) writing in peer-reviewed journals; those sources are essentially always referred to in footnotes that follow anything that is said in the text that is not common knowledge. In most cases a link is provided that allows easy referral to the original source(s) of the information. If there is not a working link, you can normally use your cursor to select a non-working link or the title of the document, then copy it (control - c usually does that), then “paste” it (control - v) into an open slot at the top of your browser, for taking you to the website where the original, authoritative source of the information can be found.

The reader is strongly encouraged to check the source(s) regarding anything he or she reads here that seems to be questionable, and to notify me of anything said in the text that does not seem to accurately represent what was said by the original source. Write to dm@pollutionaction.org. I will quickly correct anything found to be inaccurate.

Comments or questions on the above are invited, including criticisms if they are specific, and will usually receive a response. At the next link are past comments and questions from a number of readers, including eight doctors, followed by our responses. 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. Topics discussed in that section include 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

In criticisms, please point out any specific passages that you feel are not accurately based on authoritative sources (as cited) or that do not logically follow from the evidence presented. Note that the author of this article feels no obligation to present the pro-breastfeeding case as long as the medical associations and other promoters of breastfeeding fail to inform parents about the developmental toxins that are, without dispute, present in high concentrations in human milk. Please e-mail criticisms or other comments to dm@pollutionaction.org. Most will receive a reply.

For a more complete statement about the author and Pollution Action, please go to www.pollutionaction.org.