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Teresa Binstock
Researcher in Developmental & Behavioral Neuroanatomy
March 31, 2009
The peer-reviewed journal Neurotoxicology has recently published findings wherein several indoor factors including vinyl flooring (PVC and phthalates) were found to be associated with autism (1). Science writer Marla Cone has two similar but not identical articles announcing the vinyl/autism findings (2-3). The more thorough of the two articles (3) links to another environmental-factors summary by Ms. Cone (4). In each of these three summaries, either mercury is not mentioned or its role is understated.
Today's two essays by Ms. Cone (2-3) mention environmental factors:
"Previously, three studies in California have found a connection between children’s exposure to household or agricultural pesticides and autism. Rates of autism in California have increased seven-fold since 1990, a recent study found. Because genetics do not change that quickly, scientists suspect that chemical pollutants are probably playing a role. But there have been few studies attempting to pinpoint which chemicals, or combination of chemicals." (2)
Ms. Cone's rhetoric is technically correct, but concern arises that she omitted mentioning environmental mercury or arsenic and autism (eg, 5-7; see also 8-10)
Similarly, in Ms. Cone's longer essay (3), she suggests a role for other environmental factors and perhaps deliberately chose the word "chemical", which implies substances not the same as elements such as arsenic or mercury:
"The study of Swedish children is among the first to find an apparent connection between an environmental chemical and autism." (3)
With a more general statement, Ms. Cone calls attention to pesticides and other environmental factors:
"Previously, three studies in California have found a connection between children's exposure to household or agricultural pesticides and autism." (3, citing 4)
Ms. Cone's review of Hertz-Picciotto et al 2009 (a very important study) mentions mercury, especially in a context belittling thimerosal, but does not mention the several peer-reviewed findings linking environmental mercury with autism (5-7) and does not mention studies (i) describing developmental disabilities linked with thimerosal (8), or (ii) describing biomarkers related to mercury and other pollutants (eg, 9-10). Indeed, airborne mercury is associated with autism (5-7) and merits mention by reporters, especially since biomarkers have clinical significance (11-13, see also 14), and despite findings in poorly designed epidemiologic studies (15-16).
References:
1. Associations between indoor environmental factors and parental-reported autistic spectrum disorders in children 6–8 years of age
Malin Larsson et al. Neurotoxicology, In Press, Corrected Proof, Available online 10 February 2009
http://tinyurl.com/cfmyvd
Potential contributions of environmental chemicals and conditions to the etiology of Autism Spectrum Disorders are the subject of considerable current research and speculation. The present paper describes the results of a study undertaken as part of a larger project devoted to the connection between properties of the indoor environment and asthma and allergy in young Swedish children. The larger project, The Dampness in Buildings and Health (DBH) Study, began in the year 2000 with a questionnaire distributed to parents of all children 1–6 years of age in one Swedish county (DBH-I). A second, follow-up questionnaire (DBH-III) was distributed in 2005. The original survey collected information about the child, the family situation, practices such as smoking, allergic symptoms, type of residence, moisture-related problems, and type of flooring material, which included polyvinyl chloride (PVC). The 2005 survey, based on the same children, now 6–8 years of age, also asked if, during the intervening period, the child had been diagnosed with Autism, Asperger's syndrome, or Tourette's syndrome. From a total of 4779 eligible children, 72 (60 boys, 12 girls) were identified with parentally reported autism spectrum disorder. A random sample of 10 such families confirmed that the diagnoses had been made by medical professionals, in accordance with the Swedish system for monitoring children's health. An analysis of the associations between indoor environmental variables in 2000 as well as other background factors and the ASD diagnosis indicated five statistically significant variables: (1) maternal smoking; (2) male sex; (3) economic problems in the family; (4) condensation on windows, a proxy for low ventilation rate in the home; (5) PVC flooring, especially in the parents’ bedroom. In addition, airway symptoms of wheezing and physician-diagnosed asthma in the baseline investigation (2000) were associated with ASD 5 years later. Results from the second phase of the DBH-study (DBH-II) indicate PVC flooring to be one important source of airborne phthalates indoors, and that asthma and allergy prevalence are associated with phthalate concentrations in settled dust in the children's bedroom. Because these associations are among the few linking ASD with environmental variables, they warrant further and more extensive exploration.
2. Scientists find 'baffling' link between autism and vinyl flooring
Children who live in homes with vinyl floors, which can emit phthalates, are twice as likely to have autism, according to a new study by Swedish and U.S. researchers. Scientists call the discovery "intriguing and baffling." Experts suspect that genetic and environmental factors combine to cause autism, which has increased dramatically in children over the past 20 years.
By Marla Cone
Editor in Chief, Environmental Health News
March 31, 2009
http://www.environmentalhealthnews.org/ehs/news/autism-and-vinyl-flooring
3. Is Vinyl Flooring Causing Autism?
Scientists find "baffling" link between autism and the phthalates off-gassed by vinyl flooring, and other indoor air contaminants.
By Marla Cone
3.31.2009 8:38 AM
http://www.thedailygreen.com/environmental-news/latest/autism-causes-vinyl-flooring-47033101
4. Autism epidemic not caused by shifts in diagnoses; environmental factors likely
Changes in doctors' diagnoses cannot explain the sevenfold increase in autism since 1990, a new California study shows.
By Marla Cone
Editor in Chief, Environmental Health News
January 9, 2009
http://environmentalhealthnews.org/ehs/news/autism-and-environment
5. Environmental mercury release, special education rates, and autism disorder: an ecological study of Texas.
Palmer RF et al. Health Place. 2006 Jun;12(2):203-9.
The association between environmentally released mercury, special education and autism rates in Texas was investigated using data from the Texas Education Department and the United States Environmental Protection Agency. A Poisson regression analysis adjusted for school district population size, economic and demographic factors was used. There was a significant increase in the rates of special education students and autism rates associated with increases in environmentally released mercury. On average, for each 1,000 lb of environmentally released mercury, there was a 43% increase in the rate of special education services and a 61% increase in the rate of autism. The association between environmentally released mercury and special education rates were fully mediated by increased autism rates. This ecological study suggests the need for further research regarding the association between environmentally released mercury and developmental disorders such as autism. These results have implications for policy planning and cost analysis.
6. Autism spectrum disorders in relation to distribution of hazardous air pollutants in the san francisco bay area.
Windham GC et al. Environ Health Perspect. 2006 Sep;114(9):1438-44.
http://www.ehponline.org/members/2006/9120/9120.html
OBJECTIVE: To explore possible associations between autism spectrum disorders (ASD) and environmental exposures, we linked the California autism surveillance system to estimated hazardous air pollutant (HAP) concentrations compiled by the U.S. Environmental Protection Agency. METHODS: Subjects included 284 children with ASD and 657 controls, born in 1994 in the San Francisco Bay area. We assigned exposure level by census tract of birth residence for 19 chemicals we identified as potential neurotoxicants, developmental toxicants, and/or endocrine disruptors from the 1996 HAPs database. Because concentrations of many of these were highly correlated, we combined the chemicals into mechanistic and structural groups, calculating summary index scores. We calculated ASD risk in the upper quartiles of these group scores or individual chemical concentrations compared with below the median, adjusting for demographic factors. RESULTS: The adjusted odds ratios (AORs) were elevated by 50% in the top quartile of chlorinated solvents and heavy metals [95% confidence intervals (CIs) , 1.1-2.1], but not for aromatic solvents. Adjusting for these three groups simultaneously led to decreased risks for the solvents and increased risk for metals (AORs for metals: fourth quartile = 1.7 ; 95% CI, 1.0-3.0 ; third quartile = 1.95 ; 95% CI, 1.2-3.1) . The individual compounds that contributed most to these associations included mercury, cadmium, nickel, trichloroethylene, and vinyl chloride. CONCLUSIONS: Our results suggest a potential association between autism and estimated metal concentrations, and possibly solvents, in ambient air around the birth residence, requiring confirmation and more refined exposure assessment in future studies.
7. Proximity to point sources of environmental mercury release as a predictor of autism prevalence.
Palmer RF, Blanchard S, Wood R. Health Place. 2009 Mar;15(1):18-24.
The objective of this study was to determine if proximity to sources of mercury pollution in 1998 were related to autism prevalence in 2002. Autism count data from the Texas Educational Agency and environmental mercury release data from the Environmental Protection Agency were used. We found that for every 1000 pounds of industrial release, there was a corresponding 2.6% increase in autism rates (p<.05) and a 3.7% increase associated with power plant emissions(P<.05). Distances to these sources were independent predictors after adjustment for relevant covariates. For every 10 miles from industrial or power plant sources, there was an associated decreased autism Incident Risk of 2.0% and 1.4%, respectively (p<.05). While design limitations preclude interpretation of individual risk, further investigations of environmental risks to child development issues are warranted.
8. Biomarkers of environmental toxicity and susceptibility in autism.
Geier DA et al. J Neurol Sci. 2008 Sep 24. [Epub ahead of print]
Autism spectrum disorders (ASDs) may result from a combination of genetic/biochemical susceptibilities in the form of a reduced ability to excrete mercury and/or increased environmental exposure at key developmental times. Urinary porphyrins and transsulfuration metabolites in participants diagnosed with an ASD were examined. A prospective, blinded study was undertaken to evaluate a cohort of 28 participants with an ASD diagnosis for Childhood Autism Rating Scale (CARS) scores, urinary porphyrins, and transsulfuration metabolites. Testing was conducted using Vitamin Diagnostics, Inc. (CLIA-approved) and Laboratoire Philippe Auguste (ISO-approved). Participants with severe ASDs had significantly increased mercury intoxication-associated urinary porphyrins (pentacarboxyporphyrin, precoproporphyrin, and coproporphyrin) in comparison to participants with mild ASDs, whereas other urinary porphyrins were similar in both groups. Significantly decreased plasma levels of reduced glutathione (GSH), cysteine, and sulfate were observed among study participants relative to controls. In contrast, study participants had significantly increased plasma oxidized glutathione (GSSG) relative to controls. Mercury intoxication-associated urinary porphyrins were significantly correlated with increasing CARS scores and GSSG levels, whereas other urinary porphyrins did not show these relationships. The urinary porphyrin and CARS score correlations observed among study participants suggest that mercury intoxication is significantly associated with autistic symptoms. The transsulfuration abnormalities observed among study participants indicate that mercury intoxication was associated with increased oxidative stress and decreased detoxification capacity.
9. The plasma zinc/serum copper ratio as a biomarker in children with autism spectrum disorders.
Faber S et al. Biomarkers. 2009 Mar 11:1-10.
The frequency of zinc deficiency, copper toxicity and low zinc/copper in children with autism spectrum disorders (ASDs) may indicate decrement in metallothionein system functioning. A retrospective review of plasma zinc, serum copper and zinc/copper was performed on data from 230 children with autistic disorder, pervasive developmental disorder-NOS and Asperger's syndrome. The entire cohort's mean zinc level was 77.2 mug dl(-1), mean copper level was 131.5 mug dl(-1), and mean Zn/Cu was 0.608, which was below the 0.7 cut-off of the lowest 2.5% of healthy children. The plasma zinc/serum copper ratio may be a biomarker of heavy metal, particularly mercury, toxicity in children with ASDs.
10. Hepatitis B triple series vaccine and developmental disability in US children aged 1-9 years
Gallagher C, Goodman M. Toxicological & Environmental Chemistry 90(5):997-1008 2008.
This study investigated the association between vaccination with the Hepatitis B triple series vaccine prior to 2000 and developmental disability in children aged 1-9 years (n = 1824), proxied by parental report that their child receives early intervention or special education services (EIS). National Health and Nutrition Examination Survey 1999-2000 data were analyzed and adjusted for survey design by Taylor Linearization using SAS version 9.1 software, with SAS callable SUDAAN version 9.0.1. The odds of receiving EIS were approximately nine times as great for vaccinated boys (n = 46) as for unvaccinated boys (n = 7), after adjustment for confounders. This study found statistically significant evidence to suggest that boys in United States who were vaccinated with the triple series Hepatitis B vaccine, during the time period in which vaccines were manufactured with thimerosal, were more susceptible to developmental disability than were unvaccinated boys.
11. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism.
James SJ et al. Am J Clin Nutr. 2004 Dec;80(6):1611-7
http://www.ajcn.org/cgi/content/full/80/6/1611
BACKGROUND: Autism is a complex neurodevelopmental disorder that usually presents in early childhood and that is thought to be influenced by genetic and environmental factors. Although abnormal metabolism of methionine and homocysteine has been associated with other neurologic diseases, these pathways have not been evaluated in persons with autism. OBJECTIVE: The purpose of this study was to evaluate plasma concentrations of metabolites in the methionine transmethylation and transsulfuration pathways in children diagnosed with autism. DESIGN: Plasma concentrations of methionine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), adenosine, homocysteine, cystathionine, cysteine, and oxidized and reduced glutathione were measured in 20 children with autism and in 33 control children. On the basis of the abnormal metabolic profile, a targeted nutritional intervention trial with folinic acid, betaine, and methylcobalamin was initiated in a subset of the autistic children. RESULTS: Relative to the control children, the children with autism had significantly lower baseline plasma concentrations of methionine, SAM, homocysteine, cystathionine, cysteine, and total glutathione and significantly higher concentrations of SAH, adenosine, and oxidized glutathione. This metabolic profile is consistent with impaired capacity for methylation (significantly lower ratio of SAM to SAH) and increased oxidative stress (significantly lower redox ratio of reduced glutathione to oxidized glutathione) in children with autism. The intervention trial was effective in normalizing the metabolic imbalance in the autistic children. CONCLUSIONS: An increased vulnerability to oxidative stress and a decreased capacity for methylation may contribute to the development and clinical manifestation of autism.
12. A prospective study of mercury toxicity biomarkers in autistic spectrum disorders.
Geier DA, Geier MR.
J Toxicol Environ Health A. 2007 Oct;70(20):1723-30.
Porphyrins are derivatives formed in the heme synthesis pathway and porphyrins afford a measure of xenobiotic exposure. The steps in the heme pathway most vulnerable to heavy metal inhibition are uroporphyrin decarboxylase (UROD) and coproporphyrinogen oxidase (CPOX) reactions. Mercury toxicity was associated with elevations in urinary coproporphyrin (cP), pentacarboxyporphyrin (5cxP), and precoproporphyrin (prcP) (also known as keto-isocoproporphyrin) levels. Two cohorts of autistic patients in the United States and France had urine porphyrin levels associated with mercury toxicity. A prospective study of urinary porphyrin testing at LabCorp (United States) and the Laboratoire Philippe Auguste (France) involving 71 autism spectrum disorder (ASD) patients, neurotypical sibling controls, and general population controls was undertaken. ASD patients had significant elevations in urinary levels of cP, 5cxP, and prcP relative to controls, and > 50% of ASD patients had urinary cP levels more than 2 standard deviations above the mean values for neurotypical sibling controls. Significant reductions in urinary 5cxP and cP levels were observed in ASD patients following chelation. A significant correlation was found between urinary porphyrins measured at LabCorp and those measured at the Laboratoire Philippe Auguste on individual ASD patients. The established developmental neurotoxicity attributed to mercury and biochemical/genomic evidence for mercury susceptibility/toxicity in ASDs indicates a causal role for mercury. Urinary porphyrin testing is clinically available, relatively inexpensive, and noninvasive. Porphyrins need to be routinely measured in ASDs to establish if mercury toxicity is a causative factor and to evaluate the effectiveness of chelation therapy.
13. Cellular and mitochondrial glutathione redox imbalance in lymphoblastoid cells derived from children with autism.
James SJ et al. FASEB J. 2009 Mar 23. [Epub ahead of print]
Research into the metabolic phenotype of autism has been relatively unexplored despite the fact that metabolic abnormalities have been implicated in the pathophysiology of several other neurobehavioral disorders. Plasma biomarkers of oxidative stress have been reported in autistic children; however, intracellular redox status has not yet been evaluated. Lymphoblastoid cells (LCLs) derived from autistic children and unaffected controls were used to assess relative concentrations of reduced glutathione (GSH) and oxidized disulfide glutathione (GSSG) in cell extracts and isolated mitochondria as a measure of intracellular redox capacity. The results indicated that the GSH/GSSG redox ratio was decreased and percentage oxidized glutathione increased in both cytosol and mitochondria in the autism LCLs. Exposure to oxidative stress via the sulfhydryl reagent thimerosal resulted in a greater decrease in the GSH/GSSG ratio and increase in free radical generation in autism compared to control cells. Acute exposure to physiological levels of nitric oxide decreased mitochondrial membrane potential to a greater extent in the autism LCLs, although GSH/GSSG and ATP concentrations were similarly decreased in both cell lines. These results suggest that the autism LCLs exhibit a reduced glutathione reserve capacity in both cytosol and mitochondria that may compromise antioxidant defense and detoxification capacity under prooxidant conditions.-James, S. J., Rose, S., Melnyk, S., Jernigan, S., Blossom, S., Pavliv, O., Gaylor, D.W. Cellular and mitochondrial glutathione redox imbalance in lymphoblastoid cells derived from children with autism.
14. Ockman's Razor and Autism: The case for developmental neurotoxins contributing to a disease of neurodevelopment
M. Catherine DeSoto
Neurotoxicology, Available online 21 March 2009.
http://dx.doi.org/10.1016/j.neuro.2009.03.003
Much professional awareness regarding environmental triggers for ASD has been narrowly focused on a single possible exposure pathway (vaccines). Meanwhile, empirical support for environmental toxins as a broad class has been quietly accumulating. Recent research has shown that persons with ASD have comparatively higher levels of various toxins and are more likely to have reduced detoxifying ability, and, that rates of ASD may be higher in areas with greater pollution. This report documents that within the state with the highest rate of ASD, the rate is higher for schools near EPA Superfund sites, t (332) = 3.84, p = .0001. The reasons for the rise in diagnoses likely involve genetically-predisposed individuals being exposed to various environmental triggers at higher rates than in past generations.
15. Fighting the Autism-Vaccine War
By Bernadine Healy, M.D. [former director of NIH]
http://health.usnews.com/articles/health/brain-and-behavior/2008/04/10/fighting-the-autism-vaccine-war.html
16. Duane Alexander. M.D., NICHD director.
Quoted in: NIH Agency Head: Vaccine-Autism Research is "Legitimate" - by David Kirby
http://www.huffingtonpost.com/david-kirby/nih-agency-head-vaccine-a_b_170034.html
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