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 about injected mercury as reported in poorly designed
epidemiologic studies (15-16), which are rebutted (17).
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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