Cause of pesticide exposure, Parkinson's link: Low-level exposure to the pesticides disrupts cells in a way that mimics the effects of mutations known to cause Parkinson's disease -- ScienceDaily

Previous studies have found an association between two commonly used
agrochemicals (paraquat and maneb) and Parkinson's disease. Now a
professor has determined that low-level exposure to the pesticides
disrupts cells in a way that mimics the effects of mutations known to
cause Parkinson's disease. Adding the effects of the chemicals to a
predisposition for Parkinson's disease drastically increases the risk of
disease onset.

From this Paper:-
Nitration of microtubules blocks axonal mitochondrial transport in a human pluripotent stem cell model of Parkinson’s disease. The FASEB Journal, 2018; fj.201700759RR DOI: 10.1096/fj.201700759RR

Paints, pesticides, and other consumer products now add as much to air pollution as cars | Science | AAAS

Cars are no longer the top contributor to urban air pollution. That’s
the conclusion of a new study presented here at the annual meeting of
AAAS, which publishes Science, that finds pesticides,
paints, adhesives, and other consumer and industrial products add about
as much to air pollution as transportation does. For the new work,
researchers examined volatile organic compounds (VOCs). VOCs react with
air to create ozone and, separately, produce fine particulate matter,
which contributes to haze. Both of these air pollutants are health
hazards and contribute to respiratory diseases, particularly in urban
areas where emissions tend to be highest. Emissions from cars and other
automobiles have long been considered the major contributor to these
kinds of air pollutants. But the new work, which examined the chemical
productions statistics from industrial and government agencies, found
pesticides, coatings, inks, adhesives, and personal care products such
as perfumes produce more than double the emissions of cars.
That means U.S. inventories underestimate VOC emissions from these
products by as much as a factor of three while overestimating car VOC
emissions by 40%, researchers also report today in Science.
Because most people use the products that make VOCs indoors, the
researchers also compared emissions from residential and commercial
buildings to outdoor measurements in Los Angeles, California. They found
the concentration of emission compounds indoors was seven times higher
than in ambient air. That means air pollution is increasingly from
consumer and industrial products rather than from the transportation
sector. These products are used indoors where people spend most of their
time, which means their use poses a health risk that requires updated
regulations, the researchers say.

What does the environment have to do with autism? | Ensia

Folic acid may mitigate autism risk from pesticides

 "In the paper, which used data from the Childhood Autism Risks from Genetics and the Environment (CHARGE) study, researchers looked at 296 children between 2 and 5 who had been diagnosed with ASD and 220 who had developed typically. Mothers were interviewed about their household pesticide exposure during pregnancy, as well as their folic acid and B vitamin intake. The team also linked data from California Pesticide Use reports, which provide important details about agricultural spraying, with the mothers' addresses.
Mothers who took less than 800 micrograms and encountered household pesticides had a much higher estimated risk of having a child who developed an ASD than moms who took 800 micrograms of folic acid or more and were not exposed to pesticides. The associated risk increased for women exposed repeatedly. Women with low folic acid intake who were exposed to agricultural pesticides during a window from three months before conception to three months afterward also were at higher estimated risk."



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Aerial spraying to combat mosquitos linked to increased risk of autism in children

 Researchers who will present the abstract, "Aerial Pesticide Exposure Increases the Risk of Developmental Delay and Autism Spectrum Disorder," identified a swampy region in central New York where health officials use airplanes to spray pyrethroid pesticides each summer. The pesticides target mosquitos that carry the eastern equine encephalitis virus, which can cause swelling of the brain and spinal cord. They found that children living in ZIP codes in which aerial pesticide spraying has taken place each summer since 2003 were approximately 25 percent more likely to have an autism diagnosis or documented developmental delay compared to those in ZIP codes with other methods of pesticide distribution, such as manually spreading granules or using hoses or controlled droplet applicators."

Pyrethroid pesticide exposure appears to speed puberty in boys | Endocrine Society

Scientists provide first evidence that carbamates can upset circadian rhythms

 The current research focuses on two chemicals, carbaryl, the third most widely used insecticide in the U.S. but which is illegal in several countries, and carbofuran, the most toxic carbamate insecticide, which has been banned for applications on food crops for human consumption since 2009. It is still used in many countries, including Mexico and traces persist in food, plants and wildlife.
"We found that both insecticides are structurally similar to melatonin and that both showed affinity for the melatonin, MT2 receptors, that can potentially affect glucose homeostasis and insulin secretion," said Marina Popovska-Gorevski, co-author, now a scientist with Boehringer Ingelheim Pharmaceuticals, who worked in Dubocovich's lab while earning her master's degree at UB. "That means that exposure to them could put people at higher risk for diabetes and also affect sleeping patterns.""

Autism genes are selectively targeted by environmental pollutants including pesticides, heavy metals, bisphenol A, phthalates and many others in food, cosmetics or household products

The increasing incidence of autism suggests a major environmental influence. Epidemiology has implicated many candidates and genetics many susceptibility genes. Gene/environment interactions in autism were analysed using 206 autism susceptibility genes (ASG's) from the Autworks database to interrogate ∼1 million chemical/gene interactions in the comparative toxicogenomics database. Any bias towards ASG's was statistically determined for each chemical. Many suspect compounds identified in epidemiology, including tetrachlorodibenzodioxin, pesticides, particulate matter, benzo(a)pyrene, heavy metals, valproate, acetaminophen, SSRI's, cocaine, bisphenol A, phthalates, polyhalogenated biphenyls, flame retardants, diesel constituents, terbutaline and oxytocin, inter alia showed a significant degree of bias towards ASG's, as did relevant endogenous agents (retinoids, sex steroids, thyroxine, melatonin, folate, dopamine, serotonin). Numerous other suspected endocrine disruptors (over 100) selectively targeted ASG's including paraquat, atrazine and other pesticides not yet studied in autism and many compounds used in food, cosmetics or household products, including tretinoin, soy phytoestrogens, aspartame, titanium dioxide and sodium fluoride. Autism polymorphisms influence the sensitivity to some of these chemicals and these same genes play an important role in barrier function and control of respiratory cilia sweeping particulate matter from the airways. Pesticides, heavy metals and pollutants also disrupt barrier and/or ciliary function, which is regulated by sex steroids and by bitter/sweet taste receptors. Further epidemiological studies and neurodevelopmental and behavioural research is warranted to determine the relevance of a large number of suspect candidates whose addition to the environment, household, food and cosmetics might be fuelling the autism epidemic in a gene-dependent manner.

Exposure to endocrine-disrupting chemicals in the USA: a population-based disease burden and cost analysis - The Lancet Diabetes & Endocrinology

Background
Endocrine-disrupting chemicals (EDCs) contribute to disease and dysfunction and incur high associated costs (>1% of the gross domestic product [GDP] in the European Union). Exposure to EDCs varies widely between the USA and Europe because of differences in regulations and, therefore, we aimed to quantify disease burdens and related economic costs to allow comparison.

Methods
We used existing models for assessing epidemiological and toxicological studies to reach consensus on probabilities of causation for 15 exposure–response relations between substances and disorders. We used Monte Carlo methods to produce realistic probability ranges for costs across the exposure–response relation, taking into account uncertainties. Estimates were made based on population and costs in the USA in 2010. Costs for the European Union were converted to US$ (€1=$1·33).

Findings
The disease costs of EDCs were much higher in the USA than in Europe ($340 billion [2·33% of GDP] vs $217 billion [1·28%]). The difference was driven mainly by intelligence quotient (IQ) points loss and intellectual disability due to polybrominated diphenyl ethers (11 million IQ points lost and 43 000 cases costing $266 billion in the USA vs 873 000 IQ points lost and 3290 cases costing $12·6 billion in the European Union). Accounting for probability of causation, in the European Union, organophosphate pesticides were the largest contributor to costs associated with EDC exposure ($121 billion), whereas in the USA costs due to pesticides were much lower ($42 billion).

 Interpretation
EDC exposure in the USA contributes to disease and dysfunction, with annual costs taking up more than 2% of the GDP. Differences from the European Union suggest the need for improved screening for chemical disruption to endocrine systems and proactive prevention."





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Environmental risk factors for dementia: a systematic review | BMC Geriatrics | Full Text

Dementia risk reduction is a major and growing public health priority. While certain modifiable risk factors for dementia have been identified, there remains a substantial proportion of unexplained risk. There is evidence that environmental risk factors may explain some of this risk. Thus, we present the first comprehensive systematic review of environmental risk factors for dementia.

Methods 

We searched the PubMed and Web of Science databases from their inception to January 2016, bibliographies of review articles, and articles related to publically available environmental data. Articles were included if they examined the association between an environmental risk factor and dementia. Studies with another outcome (for example, cognition), a physiological measure of the exposure, case studies, animal studies, and studies of nutrition were excluded. Data were extracted from individual studies which were, in turn, appraised for methodological quality. The strength and consistency of the overall evidence for each risk factor identified was assessed.

Results

We screened 4784 studies and included 60 in the review. Risk factors were considered in six categories: air quality, toxic heavy metals, other metals, other trace elements, occupational-related exposures, and miscellaneous environmental factors. Few studies took a life course approach. There is at least moderate evidence implicating the following risk factors: air pollution; aluminium; silicon; selenium; pesticides; vitamin D deficiency; and electric and magnetic fields.

 Conclusions

Studies varied widely in size and quality and therefore we must be circumspect in our conclusions. Nevertheless, this extensive review suggests that future research could focus on a short list of environmental risk factors for dementia. Furthermore, further robust, longitudinal studies with repeated measures of environmental exposures are required to confirm these associations."

Specific Triazine Herbicides Induce Amyloid-β42 Production - IOS Press

"Proteolytic cleavage of the amyloid-β protein precursor (AβPP) by secretases leads to extracellular release of amyloid-β (Aβ) peptides. Increased production of Aβ42 over Aβ40 and aggregation into oligomers and plaques constitute an Alzheimer’s disease (AD) hallmark. Identifying products of the ‘human chemical exposome’ (HCE) able to induce Aβ42 production may be a key to understanding some of the initiating causes of AD and to generate non-genetic, chemically-induced AD animal models. A cell model was used to screen HCE libraries for Aβ42 inducers. Out of 3500+ compounds, six triazine herbicides were found that induced a β- and γ-secretases-dependent, 2–10 fold increase in the production of extracellular Aβ42 in various cell lines, primary neuronal cells, and neurons differentiated from human-induced pluripotent stem cells (iPSCs). Immunoprecipitation/mass spectrometry analyses show enhanced production of Aβ peptides cleaved at positions 42/43, and reduced production of peptides cleaved at positions 38 and lower, a characteristic of AD. Neurons derived from iPSCs obtained from a familial AD (FAD) patient (AβPP K724N) produced more Aβ42 versus Aβ40 than neurons derived from healthy controls iPSCs (AβPP WT). Triazines enhanced Aβ42 production in both control and AD neurons. Triazines also shifted the cleavage pattern of alcadeinα, another γ-secretase substrate, suggesting a direct effect of triazines on γ-secretase activity. In conclusion, several widely used triazines enhance the production of toxic, aggregation prone Aβ42/Aβ43 amyloids, suggesting the possible existence of environmental “Alzheimerogens” which may contribute to the initiation and propagation of the amyloidogenic process in late-onset AD."



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Chemicals banned decades ago linked to increased autism risk today

According to the research, children born after being exposed to the highest levels of certain compounds of the chemicals, called organochlorine chemicals, during their mother's pregnancy were roughly 80 percent more likely to be diagnosed with autism when compared to individuals with the very lowest levels of these chemicals. That also includes those who were completely unexposed.
Although production of organochlorine chemicals was banned in the United States in 1977, these compounds can remain in the environment and become absorbed in the fat of animals that humans eat, leading to exposure.
With that in mind, Kristen Lyall, ScD, assistant professor in Drexel University's A.J. Drexel Autism Institute, and her collaborators, decided to look at organochlorine chemicals during pregnancy since they can cross through the placenta and affect the fetus' neurodevelopment."

The barrier, airway particle clearance, placental and detoxification functions of autism susceptibility genes

Even taking problems of diagnosis into account, a five-fold increase in the incidence of autism in recent decades, in the absence of any known changes in the human gene pool suggests a strong environmental influence. Numerous pollutants have been implicated in epidemiological studies, including pesticides, heavy metals, industrial solvents, air pollutants, particulate matter, bisphenol A, phthalates and flame retardants. Many genes have been implicated in autism, some of which are directly related to detoxification processes. Many are also expressed prenatally in the frontal cortex when the effects of such toxins on neurodevelopment are most relevant. To gain access to the foetal brain, toxins must pass placental and blood/brain barriers and access to maternal or children's blood necessitates passage across skin, airway and intestinal barriers. Literature survey of a subset of 206 genes, defined as prime autism susceptibility candidates from an Autworks/Genotator analysis, revealed that most could be related to barrier function at blood/brain, skin, intestinal, placental or other interfaces. These genes were highly enriched in proteome datasets from blood/brain and placental trophoblast barriers and many localised to skin, intestinal, lung, umbilical and placental compartments. Many were also components of the exosomal/transcytosis pathway that is involved in the transfer of compounds across cells themselves, rather than between them. Several are involved in the control of respiratory cilia that sweep mucus and noxious particles from the airways. A key role of autism susceptibility genes may thus relate to their ability to modulate the access of numerous toxins to children, and adults and, during gestation, to the developing foetal brain.

Aerial pesticide exposure increases the risk of developmental delay and Autism spectrum disorder

BACKGROUND:

Pesticides are one environmental factor implicated in developmental delay (DD) and autism spectrum disorder (ASD). The influence of the timing and route of pesticide exposure on the risk of ASD/DD is not well defined.

OBJECTIVE: We identified an area of Central New York (NY) with unique pyrethroid pesticide (PP) exposure to study these factors. Each summer, to combat mosquito-borne encephalitis in the Cicero Swamp region, the Department of Health uses airplanes to apply PPs. In contrast, surrounding areas are exposed to standard methods of pesticide application, such as controlled droplet application, by commercial applicators. The objective of this study was to determine if the amount, route or gestational timing of pesticide exposure influenced the risk of ASD/DD.

DESIGN/METHODS: A retrospective review of records from a tertiary referral center was used to estimate the number of children with ASD/DD from 24 zip codes within Central NY from March, 2010 to March, 2015. Cases were identified using ICD-9 codes for ASD or DD at 6 affiliated pediatric clinics. To control for referral bias, rates of 4 common diagnoses were calculated for each zip code. Publicly available mandated reporting data from the Department of Environmental Conservation were used to quantify pesticide exposure (kg) among zip codes. The 2013 American Community Survey was used to quantify demographic data. Data from the 8 zip codes exposed to yearly aerial PPs were compared with 16 control zip codes.

RESULTS: There was no significant difference between aerial-exposed and control groups in number of children, overall births, premature births, poverty level, or child sex. The referral rate from aerial-exposed zip codes was lower for all 4 control diagnoses. The aerial-exposed zip codes had higher levels of total pesticide exposure (p = 0.047), but no difference in pesticide use per square km (p = 0.10). The relative risk of ASD/DD for children in zip codes with aerial spraying was 1.25 (95% CI = 1.025-1.506). ASD/DD prevalence correlated with aerial PP exposure (r = 0.58) and total pesticide exposure (r = 0.41). There was no correlation between gestational age during aerial spraying and ASD/DD prevalence (r = -0.034).

CONCLUSIONS: Exposure to pesticides is correlated with increased risk of ASD/DD. The relative risk of ASD/DD increases when PP exposure occurs through aerial application, but the gestational timing of this exposure does not influence ASD/DD risk."



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Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration : Nature Communications : Nature Publishing Group

 "Environmental factors, including pesticides, have been linked to autism and neurodegeneration risk using retrospective epidemiological studies. Here we sought to prospectively identify chemicals that share transcriptomic signatures with neurological disorders, by exposing mouse cortical neuron-enriched cultures to hundreds of chemicals commonly found in the environment and on food. We find that rotenone, a pesticide associated with Parkinson’s disease risk, and certain fungicides, including pyraclostrobin, trifloxystrobin, famoxadone and fenamidone, produce transcriptional changes in vitro that are similar to those seen in brain samples from humans with autism, advanced age and neurodegeneration (Alzheimer’s disease and Huntington’s disease). These chemicals stimulate free radical production and disrupt microtubules in neurons, effects that can be reduced by pretreating with a microtubule stabilizer, an antioxidant, or with sulforaphane. Our study provides an approach to prospectively identify environmental chemicals that transcriptionally mimic autism and other brain disorders."



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New method finds 57 pesticides in poisoned honey bees - Medical News Today

"The researchers, led by Tomasz Kiljanek of the Department of Pharmacology and Toxicology, report how they developed and validated a method for simultaneously detecting up to 200 pesticides and metabolites in honey bees."

Multi-residue method for the determination of pesticides and pesticide metabolites in honeybees by liquid and gas chromatography coupled with tandem mass spectrometry-Honeybee poisoning incidents. Kiljanek et al, 2016

Groundwater pesticide levels and the association with Parkinson disease. - PubMed - NCBI

It is unclear whether exposure to environmentally relevant levels of pesticides in groundwater is associated with an increased risk of Parkinson disease (PD). The purpose of this study was to examine the relationship between PD and pesticide levels in groundwater. This cross-sectional study included 332 971 Medicare beneficiaries, including 4207 prevalent cases of PD from the 2007 Colorado Medicare Beneficiary Database. Residential pesticide levels were estimated from a spatial model based on 286 well water samples with atrazine, simazine, alachlor, and metolachlor measurements. A logistic regression model with known PD risk factors was used to assess the association between residential groundwater pesticide levels and prevalent PD. We found that for every 1.0 µg/L of pesticide in groundwater, the risk of PD increases by 3% (odds ratio = 1.03; 95% confidence interval: 1.02-1.04) while adjusting for age, race/ethnicity, and gender suggesting that higher age-standardized PD prevalence ratios are associated with increasing levels of pesticides in groundwater.



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Pesticide found in milk decades ago may be associated with signs of Parkinson's

For the study, 449 Japanese-American men with an average age of 54 who participated in the Honolulu-Asia Aging Study were followed for more than 30 years and until death, after which autopsies were performed. Tests looked at whether participants had lost brain cells in the substantia nigra area of the brain, which occurs in Parkinson's disease and can start decades before any symptoms begin. Researchers also measured in 116 brains the amount of residue of a pesticide called heptachlor epoxide. The pesticide was found at very high levels in the milk supply in the early 1980s in Hawaii, where it was used in the pineapple industry. It was used to kill insects and was removed from use in the US around that time. The pesticide may also be found in well water.

Parkinson's Disease and Pesticides Exposure: New Findings From a Comprehensive Study in Nebraska, USA. - PubMed - NCBI

"The association between exposure to agricultural pesticides and Parkinson's Disease (PD) has long been a topic of study in the field of environmental health. This research takes advantage of the unique Nebraska PD registry and state-level crop classification data to investigate the PD-pesticides exposure relationship.

METHODS:
First, Geographic Information System and satellite remote sensing data were adopted to calculate exposure to different pesticides for Nebraska residents. An integrated spatial exploratory framework was then adopted to explore the association between PD incidence and exposure to specific pesticide ingredients at the county level.

RESULTS:
Our results reveal similarities in geographic patterns of pesticide exposure and PD incidence. The regression analyses indicate that, for most Nebraska counties, PD incidence was significantly associated with exposure to certain pesticide ingredients such as alachlor and broxomy. However, the results also suggest that factors other than pesticide exposure may help further explain the risk of PD at the county level.

CONCLUSIONS:
We found significant associations between PD incidence and exposure to different pesticide ingredients. These results have useful implications for PD prevention in Nebraska and other agricultural states in the United States."



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Environmental Obesogens | The Scientist Magazine®

"In 2005, Mike Skinner’s group at Washington State University published a disturbing observation: pregnant rats exposed to high levels of a commonly used fungicide had sons with low sperm counts as adults. When these male mice did succeed in impregnating a female, they bore sons who also had fewer sperm, and the gametes were less viable. The problem perpetuated through multiple generations, as Skinner’s lab observed the rats over several years.1

“We sat on [the results] for four years because it was a major observation, so we wanted to get as much on the mechanism as possible,” Skinner says. He and his colleagues found that altered DNA methylation patterns in the germ line were to blame.

To see if other environmental chemicals could have the same effect, they screened a host of potentially toxic chemicals: jet fuel, plastics ingredients, and more pesticides. Again, exposed animals had offspring with reproductive problems, which were passed down for generations. The researchers also saw another phenotype pop up again and again: obesity. Skinner first saw fat rats in his experiments after he’d injected females with a mixture of bisphenol A (BPA) and phthalates, substances used to make plastic products and, like the fungicide the researchers originally tested, known to be endocrine disruptors. The rats’ pups and their pups’ pups—animals that had direct exposure to the chemicals—showed other abnormalities, but were of normal weight. However, roughly 10 percent of third-generation (F3) rats descended from exposed females became obese.2"



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