Neurological and Neurodevelopmental Conditions Caused by Exposure to Pesticides and Herbicides

Many studies have found that chronic pesticide or herbicide exposure through farm work or occupational exposure causes cognitive decline, seizures, polyneuropathy, psychosis, dementia, Alz . Disease, Parkinson Disease, MS, ALS, ADHD, Autism, other neurological disorders, Diabetes, and suicide (1-7). Toxic exposures to pesticides, toxic metals, and other toxins that cause oxidative stress, neuroexcitation, and chronic inflammation have synergistic effects that are not taken into account in most studies. (1b). Organophosphate pesticides, which inhibit acetylcholinesterase enzyme-as do the drugs used in treating AD symptoms- have also been shown to lead to microtubule derangements and tau hyperphosphorylation, a hallmark of AD. (1cgh) Other mechanisms that pesticides, herbicides and other toxins have include effects on several molecular targets, such as hormones;  neurotransmitters ;  neurotrophic factors ; enzymes related to the metabolism of  beta amyloid protein , as well as inflammatory changes have been identified. (1c) In high pesticide exposure areas, an increased risk for Alzheimer’s disease, other chronic neurological conditions, seizures, polyneuropathies, affective psychosis, and higher suicides have been documented. (1k, etc.) There is much evidence linking their etiology with long-term/low-dose exposure to pesticides such as DDT(DDE), paraquat, maneb , dieldrin, pyrethroids and organophosphates. Most of these pesticides share common features, namely the ability to induce oxidative stress, mitochondrial dysfunction, α-synuclein fibrillization and neuronal cell loss. (1cefgh)

Research has shown very small amounts of Aluminum are needed to produce neurotoxicity and this criterion is satisfied through dietary Al intake. Al sequesters different transport mechanisms to actively traverse brain barriers. (2) Incremental acquisition of small amounts of Al over a lifetime favors its selective accumulation in brain tissues, and experimental evidence has repeatedly demonstrated that chronic Al intoxication reproduces neuropathological hallmarks of AD. The conclusion that Al significantly contributes to AD is built upon very solid experimental evidence. Aluminum has been shown to cause encephalopathy, anemia, and bone disease in dialyzed patients.  Aluminum also causes metabolic impairment and iron (Fe) alterations which could be a factor in neurological conditions such as dementia and Alz . Disease.

There has been a huge increase in the incidence of degenerative neurological conditions in virtually all Western countries over the last 2 decades (6a). The increase in Parkinsons and other motor neuron disease has been over 50%. The primary causes appear to be increased exposures to toxic pollutants such as toxic metals , pesticides, herbicides , POPs , PAHS , etc. resulting in oxidative damage, brain inflammation , and mitochondrial damage of free-radicals(6ab). Toxic exposures cause DNA damage and allele mutations and epigenetics is a major factor in harm from toxic exposures. Some forms of genes are more susceptible to harm from toxic exposure than others (6b1, etc .).

Clinical studies of pesticide poisonings suggest that seizures and developmental effects are more common in children than in adults. Seizures can rapidly progress to status epilepticus, contributing to mortality and, in survivors, to neuronal damage and neurological impairment. (4) Seizures and developmental effects have been documented in areas with chronic pesticide exposure. Such pesticides as thiophos , sevin , chlorpyrifos (and other chemical exposures) can inhibit an enzyme called acetyl cholinesterase. Their actions lead to hyperstimulation of cholinergic synapse in brain. Electrographic seizures are a feature of organophosphate anticholinesterase intoxication. (4be) Hyperstimulation of postsynaptic muscarine acetylcholine receptor causes increased glutamate exudation. Surexcitation of its receptors leads to neuropathological changes, which cause epileptiform activity in formed focus. Pesticides such as  parathion  and  carbaryl  cause hyperstimulation of  cholinergic receptors and an increase in excitatory  neurotransmission . Glutamatergic hyperstimulation can occur after exposure to  excitatory amino acid  toxins such as the  marine toxin domoic acid . Pesticides such as  lindane  and  strychnine  do not affect excitatory neurotransmission directly, but rather, they block the inhibitory regulation of neurotransmission by antagonism of inhibitory  GABA  and  glycine  synapses. (4d) The glufosinate ammonium herbicides are one of the most common seizurogenic pesticide classes. (4)

Other pesticides, such as DDT, permethrin, fen- valerate are able to increase the activity of potentially dependent natrium channels, that increases neutron excitability. Such pesticides during poisoning can increase seizure activity of the brain and lead to convulsive seizure in healthy individuals. (4b) Pyrethroid insecticides are neurotoxic, and the development and severity of clinical signs is proportional to the nervous tissue pyrethroid concentration(4hij). Type I pyrethroid poisoning in animal studies produces a syndrome characterized by tremors, prostration and altered startle reflexes. Type II pyrethroid poisoning in animal studies causes ataxia, seizures, convulsions, hyperactivity, choreoathetosis and profuse salivation. Type I ( bioallethrin , cismethrin , tefluthrin, bifenthrin, permethrin, etc.), Type II (deltamethrin, lambda-cyhalothrin, cyfluthrin and cypermethrin, Fenpropathrin , esfenvalerate , etc.). Small pets and fish are often poisoned by pyrethrin pesticides (4h, etc.)

Almost 20% of children in the U.S. has one or more developmental disabilities, ranging from a learning disability to a serious behavioral or emotional disorder. Scientists believe that the amount of toxic chemicals in the environment that cause developmental and neurological damage are contributing to the rise of physical and mental effects being found in children. Studies show children’s developing organs create “early windows of great vulnerability” during which exposure to pesticides can cause great damage. In the U.S., requirements for testing pesticides and other chemicals for potential developmental and learning disorders are minimal. Many types of pesticides, herbicides , toxic metals , and POPs (including DDE & HCH) have been documented (3) to commonly cause Birth Defects , Attention Deficit Hyperactivity Disorder , Autism , Developmental Delays , neurodevelopmental problems, (3a) as well as Type 1 and Type 2 Diabetes (3be)

Toxic exposures such as pesticides , GMO Foods , parasites, molds, Toxic Metals , Polycyclic aromatic hydrocarbons ( PAHs ), POPs , etc. are common and cause or are factors in autoimmune conditions such as Multiple Sclerosis (MS). There is a strong link between pesticides and autoimmune diseases . Studies have shown that farming with agricultural pesticides has been known to cause rheumatoid arthritis (RA), systemic lupus erythematosus ( SLE ), Diabetes ) Most of the common pesticides including organophosphates and carbamates, fumigants, organochlorines, pyrethroids and Chlorpyrifos have been shown to have a toxic effect on humans and are factors in autoimmune conditions . Chronic exposure to pesticides has been documented to cause degenerative neurological conditions such as Multiple Sclerosis (6).

Oxidative stress, chronic inflammation, Excitotoxicity, Glutamate Toxicity, Mitochondrial Dysfunction, etc. are all caused by exposure to toxic metals or pesticides or herbicides (5) or POPs or PAHs , or EMF radiation which are documented to be factors in Amyotrophic Lateral Sclerosis ( ALS ) that cause brain damage.

References:

(1) (a)  Neuropathological Mechanisms Associated with Pesticides in Alzheimer’s Disease , Toxics 2020 ,  8 (2), 21; & (b)Pesticides, cognitive functions and dementia: A review , Toxicology Letters, Volume 326, 15 June 2020, Pages 31-51, & (c ) Organophosphate pesticide exposure and neurodegeneration , Cortex , Volume 74 , January 2016, Pages 417-426; & (d) Systematic reviews on neurodevelopmental and neurodegenerative disorders linked to pesticide exposure : Methodological features and impact on risk assessment, Environ Int Jul-Aug 2016;92-93:657-79. & (e ) Elevated serum pesticide levels and risk for Alzheimer disease , JAMA Neurol, 2014 Mar;71(3):284-90. &

(f) Pesticides exposure as etiological factors of Parkinson's disease and other neurodegenerative diseases --a mechanistic approach, Toxicol Lett. 2014 Oct 15;230(2):85-103; & (g) Linking pesticide exposure and dementia: what is the evidence?, Toxicology, 2013 May 10;307:3-11. & (h) [Neurotoxicity of pesticides: its relationship with neurodegenerative diseases], Med Sci (Paris), & ( i ) Occupational pesticide exposure and screening tests for neurodegenerative disease among an elderly population in Costa Rica , Environ Res 2013 Jan;120:96-101; & (j) Parkinson disease and Alzheimer disease: environmental risk factors , Neurologia , Nov-Dec 2014;29(9):541-9. & (k) Association between environmental exposure to pesticides and neurodegenerative diseases , Toxicology and Applied Pharmacology, Volume 256, Issue 3, 1 November 2011, Pages 379-385; & (l) Risk of dementia and Alzheimer disease increases with occupational pesticide exposure , Nature Reviews Neurology volume  6 ,  page 353 ( 2010 ); & (m) Occupational risk factors in Alzheimer's disease: a review assessing the quality of published epidemiological studies , 2007 Nov;64(11):723-32. & (n) Neurodegenerative Diseases and Exposure to Pesticides in the Elderly , American Journal of Epidemiology , Volume 157, Issue 5, 1 March 2003, Pages 409–414,

(2) Aluminum and Alzheimer's disease: after a century of controversy, is there a plausible link? J Alz Dis. 2011;23(4):567-98, https://pubmed.ncbi.nlm.nih.gov/21157018/ ; & (b) Aluminum and Alzheimer's Disease , Adv Neuro Biol, 2017;18:183-197; & (c) Exposure to Aluminum in Daily Life and Alzheimer's Disease, Adv Exp Med Biol. 2018;1091:99-111, https://pubmed.ncbi.nlm.nih.gov/30315451/ ; & (d) Animal Model of Aluminum-Induced Alzheimer's Disease, Adv Exp Med Biol. 2018;1091:113-127

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(3)(a)Beyond Pesticides- https://www.beyondpesticides.org/resources/pesticide-induced-diseases-database/learningdevelopmental

& (b) Pesticides, Herbicides, POPs (including DDE & Hexachlorocyclohexane (HCP) and occupational exposure to pesticides associated with T1D & T2D - https://www.beyondpesticides.org/resources/pesticide-induced-diseases-database/diabetes ; & (c) Health Effects of POPs, www.myflcv.com/POPs.html ; & (d)Developmental Effects of Toxic metals[ www.myflcv.com/indexTM.html ]& (e) Toxic metals effect on enzymes results in Type I and Type II Diabetes, www.myflcv.com/diabetes.html

(4) ( a) Association between environmental exposure to pesticides and epilepsy , NeuroToxicology, Volume 68, September 2018, Pages 13-18. & (b) PESTICIDE POISONING AS A FACTOR OF SEIZURE AND EPILEPSY DEVELOPMENT , Belarusian State University, & (c ) Role of Organochlorine Pesticides in Children with Idiopathic Seizures , International Scholarly Research Notices  /  2013  / Article , & (d) Chemical toxins that cause seizures , NeuroToxicology , Volume 33, Issue 6, December 2012, Pages 1473-1475; & (e) Seizure activity post organophosphate exposure , Front Biosci (Landmark Ed). 2009 Jan 1;14: 3688-711. & (f) Organic insecticides . Anaesth Intensive Care. 2000 Feb;28(1):11-21. & (g) Seizures in patients with acute pesticide intoxication, with a focus on glufosinate ammonium , Hum Exp Toxicol . 2018 Apr;37(4):331-337. & (h) Neurotoxicology of pyrethrin and the pyrethroid insecticides. Vet Hum Toxicol . 1991 Jun;33(3):238-43. Dorman DC, Beasley VR. & (I) Toxicology of selected pesticides, drugs, and chemicals. Pyrethrin and pyrethroid insecticides , Vet Clin North Am Small Anim Pract . 1990 Mar;20(2):375-82. & (j) Poisoning due to pyrethroids . Toxicol Rev. 2005;24(2):93-106

(5) Environmental and Occupational Risk Factors of Amyotrophic Lateral Sclerosis: A Population-Based Case-Control Study , Int. J. Environ. Res. Public Health 2020 ,  17 (8), 2882;( occup . In Ag., solvents (thinners & removers ),EMF ) & (b) [ An update of human exposure and toxicity. Arch Toxicol . 2017 Feb;91(2):549-599. Mostafalou S, Abdollahi M. Pesticides; https://pubmed.ncbi.nlm.nih.gov/27722929/ ;] & (c) [ Denouement of Chemicals on Amyotrophic Lateral Sclerosis: Is Green Chemistry the Answer. Med Chem. 2020;16(8):1058-1068, Fayaz F, Pottoo FH, Sharma A. et al, https://pubmed.ncbi.nlm.nih.gov/32282307/ ;] & (d) ; [ Prospective study of chemical exposures and amyotrophic lateral sclerosis . J Neurol Neurosurg Psychiatry. 2009 May;80(5):558-61. Weisskopf MG, Morozova N, et al (formaldehyde)] https://pubmed.ncbi.nlm.nih.gov/19372290/ ; & (e) [ Clinical and Lifestyle Factors and Risk of Amyotrophic Lateral Sclerosis : A P opulation-Based Case-Control Study , Int J of Environ Res & Public Health, 2020 ,  17 (3), 857; https://www.mdpi.com/1660-4601/17/3/857/htm ]

(head trauma, professional sports, electric shock, garden use of herbicides); & (f) [ Environmental and Occupational Exposures and Amyotrophic Lateral Sclerosis in New England , Neurodegener Dis 2017;17:110-116, www.karger.com/Article/Abstract/453359 ;] (chronic exposure to toxic metals, pesticides, toxic chemicals, occupation with toxics exposure, water skiing); & (g) [ Pesticides, polychlorinated biphenyls and polycyclic aromatic hydrocarbons in cerebrospinal fluid of amyotrophic lateral sclerosis patients: a case-control study , Environ Res, May 2017, Pages 261-267, https://www.sciencedirect.com/science/article/abs/pii/S0013935116312282 ; (for older males, PCB & pDDE ); & (h) [ Association of Environmental Toxins With Amyotrophic Lateral Sclerosis, JAMA Neurol.  2016;73(7):803-811, https://jamanetwork.com/journals/jamaneurology/fullarticle/2519875 ; ] (c hronic pesticide exposure); ( i ) [ Environmental Risk Factors and Amyotrophic Lateral Sclerosis (ALS): A Case-Control Study of ALS in Michigan , PLoS One. 2014; 9(6): e101186. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076303/ ;] (application of pesticides/fertilizer in private yards or gardens); &(j) [ Are environmental exposures to selenium, heavy metals, and pesticides risk factors for amyotrophic lateral sclerosis? Reviews on Environ Health, Vol 27, 2012; https://www.degruyter.com/document/doi/10.1515/reveh-2012-0002/html ;] (pesticide exposure); & (k) [ Pesticide exposure and amyotrophic lateral sclerosis , NeuroToxicology , Volume 33, Issue 3, June 2012, Pages 457-462; https://www.sciencedirect.com/science/article/abs/pii/S0161813X12000770 ;], (positively assoc. with use of Organophosphate or Pyrethrin pesticides, herbicides, and fumigants); & (l) [ Pesticide exposure as a risk factor for amyotrophic lateral sclerosis: A meta-analysis of epidemiological studies : Pesticide exposure as a risk factor for ALS, Environmental Research, Volume 117, August 2012, Pages 112-119 , https://www.sciencedirect.com/science/article/abs/pii/S0013935112001909 ;], ( exposure to pesticides); & (m) [ Exposure to chemicals and metals and risk of amyotrophic lateral sclerosis: a systematic review, Amyothrop Lateral Scler . Oct-Dec 2009;10(5-6):302-9. https://pubmed.ncbi.nlm.nih.gov/19922117/ ; ],( pesticide exposure); & (n) [ Amyotrophic Lateral Sclerosis and Exposure to Environmental Toxins: An Australian Case-Control Study , Neuroepidemiology 2006;27:130–135. https://www.karger.com/Article/PDF/95552 ]; (herbicide/pesticide exposure & solvent/chemical exposure) ; & (o) [ Analysis of factors that modify susceptibility and rate of progression in amyotrophic lateral sclerosis (ALS), Amyotrophic Lateral Sclerosis Volume 7, 2006 - Issue 3 , https://www.tandfonline.com/doi/full/10.1080/14660820600640596 ; ],(lead & pesticide exposure); & (p) [ A gene–environment study of the paraoxonase 1 gene and pesticides in amyotrophic lateral sclerosis , NeuroToxicology , Volume 28, Issue 3, May 2007, Pages 532-540 ; https://www.sciencedirect.com/science/article/abs/pii/S0161813X06003007 ;], ( The enzyme paraoxonase 1 (PON1) detoxifies organophosphates and the efficacy of this enzyme varies with polymorphisms in the PON1 gene. The  PON1  promoter allele −108t, which reduces  PON1  expression, was strongly associated with SALS.); & (n) [ Increased incidence of FMO1 gene single nucleotide polymorphisms in sporadic amyotrophic lateral sclerosis , Amyotroph Lateral Sclerosis, 2006 Dec;7(4):227-34; https://pubmed.ncbi.nlm.nih.gov/17127561/ ;], ((FMO) represent a gene family involved in the oxidative metabolism of a variety of xenobiotics, pesticides and drugs. specific allelic variants of the FMO1 gene with lower buffering capacity appear to be associated to susceptibility to develop ALS.)

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(6) (a) The Toxics Connection to Parkinson’s Disease, www.myflcv.com/Parkins.html

(b) Pesticides, Herbicides, and Parkinson’s- (1) Autoimmunity plays a role in Parkinson's disease, study suggests, Science News, April 20, 2020; & Gene Variants May Affect PD Risk After Pesticide Exposure, Medscape, Allergy & Immunology , Oct 20, 2020, https://www.medscape.com/viewarticle/939411#vp_1

&(2) [ Glyphosate exposure exacerbates the dopaminergic neurotoxicity in the mouse brain after repeated administration of MPTP, Neuroscience Letters , Volume 730 , 21 June 2020, 135032], & (3 ) Association between environmental exposure to pesticides and neurodegenerative diseases , Toxicology and Applied Pharmacology, Volume 256, Issue 3, 1 November 2011, Pages 379-385. https://www.sciencedirect.com/science/article/abs/pii/S0041008X1100175X?via%3Dihub ; & (4 ) Occupational Exposures and Neurodegenerative Diseases-A Systematic Literature Review and Meta-Analyses . Int J Environ Res Public Health. 2019 Jan 26;16(3):337. Gunnarsson LG, Bodin L. ( Lead,EMF ,Pesticides );