Retrospectivein utero exposure assessment of PCBs using preserved umbilical cords and its application to case-control comparison

Otake, Takamitsu; Yoshinaga, Jun; Seki, Yoshie; Matsumura, T.; Watanabe, Keiichiro; Ishijima, Michiko; Kato, Nobuo

doi:10.1007/bf02898144

Cited by 6 publications

(3 citation statements)

References 14 publications

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“…The first study reported that 17 children with ASD and 7 healthy siblings had similar concentrations of PCBs in umbilical cord samples. 139 The second study examined post-mortem brain samples and measured 7 polybrominated diphenyl ether and 7 PCB congeners; only one congener, PCB95, was associated with a genetic form of ASD (32 children with 15q11–13 duplications/deletions and other genetic syndromes) but this finding was not observed in 32 individuals with idiopathic ASD or 43 controls. 140 These two studies do not support a strong association between biomarkers of PCBs and ASD, although they are limited by small sample sizes.…”

Section: Resultsmentioning

confidence: 99%

Environmental toxicants and autism spectrum disorders: a systematic review

Rossignol¹,

2014

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Although the involvement of genetic abnormalities in autism spectrum disorders (ASD) is well-accepted, recent studies point to an equal contribution by environmental factors, particularly environmental toxicants. However, these toxicant-related studies in ASD have not been systematically reviewed to date. Therefore, we compiled publications investigating potential associations between environmental toxicants and ASD and arranged these publications into the following three categories: (a) studies examining estimated toxicant exposures in the environment during the preconceptional, gestational and early childhood periods; (b) studies investigating biomarkers of toxicants; and (c) studies examining potential genetic susceptibilities to toxicants. A literature search of nine electronic scientific databases through November 2013 was performed. In the first category examining ASD risk and estimated toxicant exposures in the environment, the majority of studies (34/37; 92%) reported an association. Most of these studies were retrospective case–control, ecological or prospective cohort studies, although a few had weaker study designs (for example, case reports or series). Toxicants implicated in ASD included pesticides, phthalates, polychlorinated biphenyls (PCBs), solvents, toxic waste sites, air pollutants and heavy metals, with the strongest evidence found for air pollutants and pesticides. Gestational exposure to methylmercury (through fish exposure, one study) and childhood exposure to pollutants in water supplies (two studies) were not found to be associated with ASD risk. In the second category of studies investigating biomarkers of toxicants and ASD, a large number was dedicated to examining heavy metals. Such studies demonstrated mixed findings, with only 19 of 40 (47%) case–control studies reporting higher concentrations of heavy metals in blood, urine, hair, brain or teeth of children with ASD compared with controls. Other biomarker studies reported that solvent, phthalate and pesticide levels were associated with ASD, whereas PCB studies were mixed. Seven studies reported a relationship between autism severity and heavy metal biomarkers, suggesting evidence of a dose–effect relationship. Overall, the evidence linking biomarkers of toxicants with ASD (the second category) was weaker compared with the evidence associating estimated exposures to toxicants in the environment and ASD risk (the first category) because many of the biomarker studies contained small sample sizes and the relationships between biomarkers and ASD were inconsistent across studies. Regarding the third category of studies investigating potential genetic susceptibilities to toxicants, 10 unique studies examined polymorphisms in genes associated with increased susceptibilities to toxicants, with 8 studies reporting that such polymorphisms were more common in ASD individuals (or their mothers, 1 study) compared with controls (one study examined multiple polymorphisms). Genes implicated in these studies included paraoxonase (PON1, three of five...

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Section: Resultsmentioning

confidence: 99%

Environmental toxicants and autism spectrum disorders: a systematic review

Rossignol¹,

2014

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“…Mitchell et al [ 26 ] examined post-mortem brain samples of children with autism and other neurodevelopmental disorders and found elevated PCB levels in brains of subjects with 15q11-q13 duplication, which is one genetic factor in autism, but not in subjects with autism of unknown aetiology. Otake and coworkers [ 27 ] compared PCB levels in preserved samples of umbilical cords from typically developing children and those with an ASC but failed to show significant differences between the two groups. However, sample sizes were very small and contamination of cord samples could not be excluded.…”

Section: Introductionmentioning

confidence: 99%

Influence of Low-Level Prenatal Exposure to PCDD/Fs and PCBs on Empathizing, Systemizing and Autistic Traits: Results from the Duisburg Birth Cohort Study

et al. 2015

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BackgroundPolychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) are assumed to act as endocrine disruptor chemicals. Prenatal exposure to these pollutants might influence fetal steroid hormone levels, which are thought to be related to sex-typical development and autistic traits.ObjectivesWe examined associations of prenatal levels of PCDD/Fs and PCBs with autism traits and sex-typical behaviour in childhood.MethodsWe measured levels of PCDD/Fs and PCBs in maternal blood samples during pregnancy using gas chromatography/high-resolution mass spectrometry. Sex-typical behaviour was assessed at 9 years of age (n = 96) and autistic traits at 10 years of age using the Social Responsiveness Scale (SRS; n = 100). Multiple regression analyses were conducted to estimate the associations between prenatal exposure and outcome variables.ResultsBlood concentrations (WHO2005-TEq) of ƩPCDD/Fs ranged from 2.93–46.45 pg/g lipid base (median = 12.91 pg/g lipid base) and concentrations of ƩPCBs were in the range of 1.24–25.47 pg/g lipid base (median = 6.85 pg/g lipid base) which is within the range of German background exposure. We found significant negative associations between PCDD/F levels in maternal blood and SRS scores in the whole group (β = -6.66, p < .05), in girls (β = -10.98, p < .05) and, in one SRS subscale, in boys (β = -6.86, p < .05). For PCB levels, associations with one SRS subscale were significant for the whole study group as were associations with two subscales in girls. We did not find significant associations between PCDD/F or PCB levels and sex-typical behaviour for either sex.ConclusionsIn an earlier part of this study, prenatal exposure to PCDD/Fs and PCBs was found to be associated with lower testosterone levels, therefore, our findings are consistent with the idea that autism spectrum conditions are related to fetal androgen levels. Several possible mechanisms, through which PCDD/Fs and PCBs might influence autistic behaviour, are discussed.

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“…• Mercury [45][46][47][48][49][50][51][52] • Air pollution [53][54][55][56][57] • Aluminum vaccine adjuvants [2,37] • Coproporphyrin [58] • Chlorpyrifos [59] • Glyphosate [60] • Phthalates [61,62] • PBDEs [63,64] • PCBs [64,65] • Electromagnetic frequencies [66] • Industrial chemical [67,68] • Acetaminophen exposure after vaccination [69][70][71][72][73] The Numerous studies have revealed that metal toxicity is increased in individuals with ASDs [74].…”

Section: • Valproic Acidmentioning

confidence: 99%

Autism is an Acquired Cellular Detoxification Deficiency Syndrome with Heterogeneous Genetic Predisposition

Lw¹

2018

Autism Open Access

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Neurodevelopmental disorders, including autism spectrum disorders, have a complex biological and medical basis involving diverse genetic risk and myriad environmental exposures. Teasing apart the role of specific stressors is made challenging due to the large number of apparently contributing associations, gene x environment interactions and phenomimicry. Historically, these conditions have been rare, making causality assessment at the population level infeasible. Only a few vaccines have been tested for association with autism, and it has been shown that improved diagnosis only explains a percentage of the increase in diagnosis. Now the rates are so high in some countries that public school programs cannot handle to large numbers of special needs students, and professionals are quitting their jobs due to security concerns. Here, I present a mechanistic biomedical process model (theory) of the pathophysiology of autism that reconciles the apparent paradox between the high degree of causal heterogeneity in environmental toxins, the absence of common "autism genes" and the high degree of genetic concordance (heritability) of ASD and ASD-like traits. In brief, the environmental toxin sampling liability for ASD varies among families involving different local exposures following injury to normal cellular endoplasmic detoxification and mitochondrial processes from toxic metals. The literature strongly supports that autism is most accurately seen as an acquired cellular detoxification deficiency syndrome with heterogeneous genetic predisposition that manifests pathophysiologic consequences of accumulated, runaway cellular toxicity. At a more general level, it is a form of a toxicant-induced loss of tolerance of toxins, and of chronic and sustained ER overload ("ER hyperstress"), contributing to neuronal and glial apoptosis via the unfolded protein response (UPR). Inherited risk of impaired cellular detoxification and circulating metal re-toxification in neurons and glial cells accompanied by chronic UPR is key. This model explains the aberrant protein disorder observed in ASD; the great diversity of genes that are found to have low, but real contributions to ASD risk and the sensitivity of individuals with ASD to environmental toxins. The hindrance of detoxification and loss of cellular energetics leads to apoptosis, release of cytokines and chronic neuroinflammation and microglial activation, all observed hallmarks of ASD. Interference with the development of normal complex (redundant) synapses leads to a pathological variation in neuronal differentiation, axon and dendrite outgrowth, and synaptic protein expression. The most general outcomes are overall simplification of gross synaptic anatomy and, neurofunctionally, a loss of inhibitory feedback and aberrations in long-term connections between distant regions of the brain. Failed resolution of the ER stress response leads to redistribution of neurotoxic metals, and the impaired neurocellular processes lead to subsequent accumulation of a variety of additional types o...

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Retrospectivein utero exposure assessment of PCBs using preserved umbilical cords and its application to case-control comparison

Cited by 6 publications

References 14 publications

Environmental toxicants and autism spectrum disorders: a systematic review

Environmental toxicants and autism spectrum disorders: a systematic review

Influence of Low-Level Prenatal Exposure to PCDD/Fs and PCBs on Empathizing, Systemizing and Autistic Traits: Results from the Duisburg Birth Cohort Study

Autism is an Acquired Cellular Detoxification Deficiency Syndrome with Heterogeneous Genetic Predisposition

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