Environmental Exposure to Iron, Manganese, and Pesticides: A possible cause of Parkinson's Disease

Abstract

Parkinson's disease has been linked to many environmental causes such as pesticides, iron, and manganese (Mn); Parkinson's disease (PD) affects millions of people across the United States. The causation of this disease could be linked to iron and manganese. Many studies look at exposure factors such as the chemical dieldrin. People who live in rural areas are more susceptible to the risk of PD; this could occur through the drinking of contaminated water or extensive exposure to pesticides. The study of welding and the hazards of the fumes that are produced; could pose a link to PD.

Introduction

Parkinson's disease (PD) causes are unknown, but there are suggestions that contributing factors maybe due to pesticide contamination and chemical contamination such as manganese or iron. The role of the environment show's that people who live in rural areas are more susceptible to the risk of PD through drinking contaminated well water that contain pesticides (Gorrell, DiMonte, and Graham, 1998). Millions of people are affected by PD across the United States; it's a disease that ca n rob an individual of their mobility. Most people are unaware what Parkinson's disease really is and the origins of the disease.

Statement of Problem

Toxins have been known to cause serious environmental problems and health problems. The use of pesticides has had a major impact on the health of many people across the United States. Other chemicals that are linked to PD are iron and paraquat and exposure of these chemicals are considered environmental risk factors (Peng, Peng, Stevenson, Doctrow, and Anderson, 2007, p 6914).

Significance of the Problem

In many studies it has been determined that fumes from welding rods which is known to contain the following elements:  Manganese (Mn), Zinc (Zn), Lead(Pb), Arsenic(As), Calcium(Ca), Sulfur(S), Chromium(Cr), Fluoride(F), and Hafnium(HF) (Racette, Minnich, Moerlein, Mink, Videen, and Perlmutter, 2001 p 8). Other elements such as aluminum, copper, and iron are linked to PD (Rajput 2001, p 4). The average age for the onset of PD is 55 and 5% of those are diagnosed with the disease before the age of 55 years.

Literature Review

In California; farmers use more than 250 million pounds of pesticides(Yesavage, Sheikh, Neda, Murphy, O'Hara Hierhelzer 2006 et al., p 32). This study determined whether wind blown from contaminated areas of pesticides sites were contributors to the high incidence of PD in various California communities. In this study a clear correlation between PD and pesticides (Yesavage et al., p 34). There were other areas that were contributing factors to PD; such as Mn.

Manganese is a dietary element that is a recommended nutritional intake of 2 to 5 mg/day (Jankevic 2005, p 2022). In a study of 250 patients that already had contracted PD; it was determined that out of 388 individuals in the control group; the higher the iron intake in conjunction with Mn would increase the risk of PD (Jankevic 2004). One of the elements that was found in an autopsy of a patient were the use of excessive amounts of iron located in the substantia nigra (SN) that would be associated with PD (Peng, Peng, Stevenson, Doctrow, and Anderson 2007, p 6914). Another issue is people living in areas that were known for having well water as a means of drinking water; had a high potential of exposure to PD causing contamination (Peng 2007, et al., p 6914).

Pesticide chemicals that were found in autopsied brains were at an elevated amount of organochlorine pesticide dieldrin (Richardson, Candle, Wang, Dean, Pennell, and Miller 2006, p 976). The chemical dieldrin; is no longer used but traces of this chemical is still present; dieldrin has been found in breast milk of 1,436 women living in America (Richardson 2006 et al., p 976). There is evidence that exposure to PD begins at an early age; maybe at the beginning of life at the neonatal stage.

Environmental factors of dopamine transporters (DAT) and vesicular monoamine transports 2 (VMAT2) may increase the susceptibility of dopamine neuronal in degeneration of PD (Richarson et al., p 983). Pesticides use among Californian was very high; 250 million pounds of pesticides were used annually (Ritz and Yu 2000, p 323). In California; 10,000 workers applied agricultural products which required a monitoring of their blood cholinesterase levels; due to excessive exposure. The assessment of exposure was done by counties by way of countywide per square mile by the usage of restricted pesticides in daily farming activities (Ritz and Yu 2000, p 324). Ritz and Yu 2000, p 324, classified 15 counties as high; 9 counties as moderate, and 7 counties as low; and 14 other counties as none or minimal users of agricultural pesticides.

A logistic regression analyst was used for this study with an odds ratio (OR) of 95% confidence interval (CI) for a crude adjustment. Death rates using PD as the cause of death was were 19% to 47% higher in counties that used restricted pesticides (Ritz and Yu, p 325). Adjusting for race, gender, place of birth, age, and education; for people living in counties for more than 40 years who died from PD from 1989-1994; and the prevalence of odds ratios (POR) for various restricted-pesticide use counties and those of counties that never used pesticides; there were 1.52, (95% CI: 1.35-1.72), 1.49 (95%CI: 1.31-1.69), and 1.49 (95%CI: 1.30-1.71) (Table 2) (Ritz and Yu, p 326).

Table 2 Prevalence odds ratios (POR) and (95% confidence interval (CI) for Parkinson's

disease as the underlying cause of death (ICD - 9.332) compared to ischemic heart disease

deaths (ICD-9 410-414) in California by county pesticide use; 1984-1994.

_____________________________________________________________________  

                           1989-                                                                     1984-                       

                                            POR                                                  POR                              

Risk     No. of          Crude             Adjusted          No. of      Crude       Adjusted

Factor   Cases           (95% CI)        (95% CI)         Cases      (95% a >) (95% CI)

_______________________________________________________________________

_______________________________________________________________________

County

Pesticide

use

                                                         _______________

No                      137              1.00                    1.00      981    1.0                 1.0

No                      133              1.55                       0        870       0                    0

moderate          1137                1.56

                                                 1.44                                         1.40              1.37                    

high                    703                1.42                 1.45       403    123              1.19 

1.59)             (1.09-1.38)          (1.06-1.34)

Total N

_____________________________________________________________________

cases                  4533                                                      2983

controls          259,99                                                  238,462

_____________________________________________________________________

http://ije.oxfordjournals.org/cgi/reprint/29/2/323  

As part of this study logistical regression was used along with a proportional odd mortality studies which was used as an estimate for odds ratio (OR) and a 95% CI for pesticide use as an adjusted rate related to PD (Ritz and Yu, p 325). Also noted is the higher the education the more susceptible those individuals were in contracting PD. The prevalence of OR with a 95% CI for PD; there were 703 reported cases with a 95% CI 1.42 adjusted to (1.45) in 1989-1994. The California study found an increase level of PD in counties that used pesticides. The may be a possible chemical link to Parkinson's disease. The possibility as previously stated of manganese being a link to PD  could be a valid one.

2000; from the Movement Disorders Center located at Washington University School of Medicine in St. Louis, MO (Racette, Minnich, Moerlein, Mink, Videen, and Perlmutter 2001, p 9). The welders in this study reported how many hous they worked daily, how many years they worked, how much exposure to welding before the onset of Parkinsonism symptoms (Racette 2001 et al., p 9). As the study of welders progressed; a control group of 100 patients were used; who were similar in nature to the 15 welders. The second group that was chosen for this study had PD; six patients that had similar characteristic such as age and sex (Racette et al.) and whether are not they had Parkinson's disease. The two-tailed test, unpaired student's t-test was used to compare age at onset and how long did the group have PD. The chi-square analysis was used to determine the frequency of the control group and welders as stated by Racette et al. p 9).

When a comparison was done of the 15 welders against a control group it was determined that idiopathic PD; there wasn't a great difference except for the age difference, (i.e., the control group had a much younger age) at the beginning stages of PD. Upon further study Racette et al., p 12; believed that the exposure to fumes from welding may act as a precursor to PD and other chemical elements that comprise the fumes may also be the cause of PD.

Parkinson's disease is a neurodegenerative disease where the dopaminergic neurons; substantia nigra pars compacta (SNpc) (Peng 2007, p 6914). In 1817 a British physician by the name of James Parkinson; notice people that had problems walking, talking, and just performing daily activities; which lead him to study the behavior of individuals with this disorder (Parkinson, 2007).

Individuals with PD usually end up being administered various types of medication to control various symptoms. It is very important to individuals administering treatment to PD patient that they keep abreast of the different types of medications and the possibility of drug interactions (Parkinson's Disease Foundation, Inc, 2008) (PDFI). Some of the medications that are used for treatment are: Carbidopa/Levodopa, Dopamine agonists, Anticholinergics, and MAO-B inhibitors see Table 3 - Table 8 (PDFI). The drug carbidopa/levodopa (Sinemet©, 2008) substance when used; converts into dopamine by an enzyme in the brain (PDFI). The drug levodopa is the most well known drug in existence today for Parkinson's disease. In the tables that follow are variables of treatment; depending on symptoms and presentation (PDFI, 2008).

Table 3

Stalevo© (carbidopa, levodopa and entacapone) is a combination tablet for patients who experience end-of-dose "wearing off." The tablet combines carbidopa/levodopa with entacapone. While carbidopa reduces the side effects of levodopa, entacapone extends the time levodopa is active in the  (up to 10 percent longer). The same drugs that interact with carbidopa/levodopa and entacapone interact with Stalevo©. Used by permission from Parkinson's Disease Foundation, Inc. Retrieved on May 18, 2008 from http://www.pdf.org/aboutPD/med_treatment.cfm  

Table 4

Dopamine agonists are drugs that stimulate the parts of the human brain that receive dopamine. In effect, the brain "thinks" it is receiving dopamine, so these drugs help satisfy the brain's need for dopamine. Dopamine agonists can be taken alone or in combination with medications containing lebvodopa.  Agonists available in the United States include bromocriptine (Parlodel©). In March 2007, the dopamine agonist pergolide (Permax) was pulled from the manufacturer of Neupro© (rotigotine transdermal system), recalled the drug because of concern of a deviation from approve product standards that has apparently reduced the effectiveness of the treatment. Consultt a doctor before taking any of the following to avoid possible interactions: alcohol, anti-psychotics, medications that lower blood pressure, Navane© (thiothixene), Taractan© (chlorprothixene), Haldol© (haloperidol), Reglan© (metoclopramide), phenothiazines, thiozanthenes, cimetidine, phenothiazines, butyrophenones, Cipro© and benzodiazepines.      

  Used by permission from Parkinson's Disease Foundation, Inc. Retrieved on May 18,2008 from http://www.pdf.org/About/PD/med_treatment.cfm

Table 5

    Anticholinergics(trihexphenidyl, benziropine mesylate, procyclidine, etc) do not act directly on the dopaminergic

    system. Instead they decrease the activity of another neurotransmitter that controls movement; called acetylcholine, to

    balance out the production of dopamine and acetylcholine. In general, mild PD that consists of tremor at rest can often

    be treated initially with anticholinergic agents.  Adverse effects of these drugs include blurred vision, dry mouth and

    urinary retention. Anticholinergics may be contraindicated in older patients because they can cause confusion and        

    Haldol©, Thorazine©, Symmetrel©, Cllozaril©, and alcohol

    Used by permission from Parkinson's Disease, Inc. Retrieved on May 18, 2008

    http://www.pdf.org/AboutPD/med_treatment.cfm

Table 6

MAO-B inhibitors© such as selegiline or deprenyl (Eldpryl©) are used to block an enzyme in the brain that breaks down levodopa. They have been shown to delay the need for Sinemet© when prescribed in the earliest stage of Parkinson's, and have also been approved for use in later stages of the disease to boost the effects of Sinemet©. Elderpryl© may interact with anti-depressants, narcotic pain killers and decongestants. Check with a doctor before taking any new medications.    

    Used by permission from Parkinson's Disease Foundation, Inc. Retrieved on May 18, 2008 from:

     http://www.pdf.org/AboutPD/med_treatment.cfm  

Table 7

COMT Inhibitors© such as entacapone (Comtan©) represent a different class of Parkinson's medications and they must be taken with levodopa. COMT inhibitors prolong symptom relief by blocking the action of an enzymne which breaks down levodopa, allowing a larger amount of levodopa to reach the brain, which raises the dopamine level. This helps provide a more stable, constant supply of levodopa. 

Table 8

     Used by permission from Parkinson's Disease Foundation, Inc. Retrieved on May 18, 2008 from:

     http://www.pdf.org/AboutPD/med_treatment.cfm

The material safety data sheet (MSDS) was introduced for workers and emergency personnel to assist in the proper procedural method in handling and working with different hazardous substances (MSDS, 2008). The material safety data sheet is for employees whom work around or with hazardous material and for the use of emergency responders in the event of an emergency and a need to know what chemicals were involved. Manganese is chemical substance that's been considered as a cause of PD. Manganese (Mn) poisoning from welding; many physicians are unaware of these findings and what is stated in a MSDS. The following are synmptoms of Mn poisoning:

     1. There may be tremors, shakes , loss of balance, slowed movement, walking problems, impotency, slurred speech, extreme drowsiness or nighttime leg cramps (International Brotherhood of Electrical Workers, 2003) (IBEW).

The above symptoms may be similar in nature for many welders and is probably mistaken for Parkinson's disease, Lou Gehrig's disease (ALS) or Multiple sclerosis (MS) (IBEW).

The Occupational Safety and Health Administration (OSHA) created by the Occupatyional Safety and Health Act of 1970 (Centers for Disease Control and Prevention, 2008 (CDC)).

The National Institute for Occupational Safety and Health (NIOSH) and the Occupational Safety and Health Administration (OSHA) were both created by the Occupational Safety and Health Act of 1970 (CDC, 2008).

Conclusion and Recommendation

Pesticides do show a linkage of contracting PD and the chemical exposure to pesticides. Individuals that mixed or applied pesticides; there was a positive association in the amount of incident of PD (Kamel et al., p 368). Parkinson's disease will be on the rise in the United States by an estimated increase of 1.3 million people by the year 2040 (Muir and Zearac 2001, p 888). The House Appropriations Committee would like for the National Institute of Environmental Health Sciences (NIEHS) to continue funding research into Parkinson's disease environmental influences (NIEHS, 2007). The NIEHS continue to make Parkinson's disease and other neurodegenerative diseases there priority in which $2 million dollars is available under program announcement, PAS 03-160, "Gene-Environmental Interactions in Neurodegenerative Disease," and the national network of the Collabortive Centers for Parkinson's Disease Environmental Reasearch (CCPDER) (NIEHS). Through the continued support of NIEHS in the study of Parkingson's disease and the collaboration with (CCPDER) to facilitate data sharing with other epidemiologist and improvement of identifying environmental toxicants will assist in as better collaborative effort (NIEHS, 2007).

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