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CFS and FMS Research
Organochlorine Pesticides and CFS
At the moment, CFS is essentially diagnosed by excluding all other possible causes of fatigue. The major problem with this approach is that doctors are often forced to diagnose patients on the basis of symptoms alone.
The CFS exclusion criteria relating to exposure to toxic chemicals depend on the historical report of the patient and do not consider those who have unknowingly been exposed to toxic agents. Consequently, any testing for toxins as part of the diagnostic process is usually very limited.
Solvents and organophosphate pesticides are rapidly excreted by the body. Therefore, corresponding blood serum levels can therefore only be validly estimated immediately after exposure (1).
It is possible, however, to measure persistent organochlorine molecules such as hexachloro-benzene (HCB) and dichlorodiphenyl-trichloroethane (DDT) in serum or biopsy samples.
DDT and HCB are chlorinated hydrocarbon pesticides that are an extremely stable group of lipophilic compounds. These have been used extensively around the world for pest control purposes since the early 1940's (1). These pesticides do not readily degrade in the environment and tend to accumulate in the food chain. © Bioscreen, CPRU, S Ashton and F Bartosy 1999 - 2001
Chlorinated hydrocarbons can be absorbed into the body in a number of ways that include:
1. ingestion
2. absorption through the skin.
3. inhalation (2).
Due to their lipophilic nature, these organochlorines accumulate in the cell membranes where they can alter membrane integrity and inhibit functional membrane-bound proteins (3,4). The organochlorines accumulate at high levels in fatty tissues (5,6). They can also cross the blood brain barrier where they may cause neurological problems (1).
References
1. Joy, R.M. (1993) Chlorinated hydrocarbon pesticides, in: Pesticides and neurological diseases, 2nd edition, (Ed. D.J. Ecobichon and R.M. Joy), CRC Press, London.
2. Srivastava, A.K., Gupta, B.N., Mathur, A.K., Mathur, N., Mahendra, P.N. and Bharti, R.S. (1991) The clinical and biochemical study of pesticide sprayers. Human and Experimental Toxicology, 10, 279-283.
3. Cascorbi, I. and Foret, M. (1990) Interaction of Xenobiotics on the glucose-transport system and the Na+/K+-ATPase of human skin fibroblasts. Ecotoxicology and Environmental Safety, 21, 38-46.
4. Foret, M. and Ahlers, J. (1988) Effects of phenol's on growth rate and adenosine uptake of CHO cells. Ecotoxicology and Environmental Safety 16, 303-309.
5. Kanja, L.W., Skaare, J.U., Ojwang, S.B.O. and Maitai, C.K. (1992) A comparison of organochlorine pesticide residues in maternal adipose tissue, maternal blood, cord blood and human milk from mother/infant pairs. Arch. Environ. Contam. 22, 21-24.
6. Mes, J. (1992) Organochlorine residues in human blood and biopsy fat and their relationship. Bull. Environ. Contam. Toxicol. 48, 815-820.
The sources of these toxic chemicals are often difficult to trace. However, it is likely that occupational or environmental contamination is responsible for many cases of pesticide exposure. The detection of DDE in all subjects examined is consistent with the widespread use of DDT in Australia (1). (Note: DDE is a derivative of DDT.)
Hexachlorobenzene (HCB) has also been used in Australia as a fungicide for the protection of grain in storage (7). It usually occurs as a contaminant in the production of other chlorinated solvents (eg carbon tetrachloride) and in the production of nitroso-rubber for tyres (7).
HCB and DDT are deposited in animal fats where they are very persistent. These animal fatty tissues comprise the major dietary source of organochlorines in Australia (8).
Symptoms developed from prolonged low level exposure to organochlorine pesticides may be very gradual in onset. Therefore, these symptoms may not necessarily be associated with exposure to toxins. © Bioscreen, CPRU, S Ashton and F Bartosy 1999 - 2001
However, people who work with insecticides have been found to have an increased risk of mental disorders including neurotic, depressive and sleep disorders and an acute reaction to stress (9).
Other reported effects of organochlorine exposures include:
1. An increased risk of breast cancer (10)
2. Impairment of immune function (11)
3. Development of endometriosis (12)
4. A greater risk of chromosome aberrations (13)
5. Decreases in male fertility levels (14)
6. An increased risk of still births and congenital defects in the children of pesticide-exposed males (14).
References:
1) Joy, R.M. (1993) Chlorinated hydrocarbon pesticides, in: Pesticides and neurological diseases, 2nd edition, (Ed. D.J. Ecobichon and R.M. Joy), CRC Press, London.
7) Courtney, K.D. (1979) Hexachlorobenzene (HCB): A review. Environmental Research 20, 225-266.
8) Ahmad, N., Harsas, W., Marolt, R.S., Morton, M. and Pollak, J.K. (1988) Total DDT and Dieldrin content of human adipose tissue. Bull. Environ. Contam.Toxicol. 41: 802-808.
9) de Jong, G. (1991) Long term health effects of aldrin and dieldrin. Toxicology Letters Supplement, Elsevier Science Publishers B.V., Amsterdam.
10) Wolfe, M.S., Toniolo, P.G., Lee, E.W., Rivera, M. and Dubin, N. (1993) Blood levels of organochlorine residues and risk of breast cancer. Journal of the National Cancer Institute, 85, 648-652.
11) Neubert, R., Jacob-M(ller, U., Helge, H., Stahlmann, R. and Neubert, D. (1991) Polyhalogenated dibenzo-p-dioxins and dibenzofurans and the immune system. 2. In vitro effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on lymphocytes of venous blood from man and a non-human primate (Callithrix jacchus). Arch. Toxicol. 65, 213-219.
12) Rier, S.E., Martin, D.C., Bowman, R.E., Dmowski, W.P. and Becker, J.L.(1993) Endometriosis in Rhesus monkeys (Macaca mulatta) following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Fundamental and Applied Toxicology, 21, 433-441.
13) Kourakis, A., Mouratidou, M., Kokkinos, G. Barbouti, A., Kotsis, A., Mourelatos, D. and Dozi-Vassiliades, J. (1992) Frequencies of chromosomal aberrations in pesticide sprayers working in plastic green houses. Mutation Research, 279, 145-148.
14) Rupa, D.S., Reddy, P.P. and Reddi, O.S. (1991) Reproductive performance in population exposed to pesticides in cotton fields in India. Environmental Research, 55, 123-128.
CPRU References
1. Dunstan RH, Donohoe M, Taylor W, Roberts TK, Murdoch RN & Watkins JA (1995) Chlorinated hydrocarbons and chronic fatigue syndrome Med J Aust 163:294-297
2. Dunstan RH, Roberts TK, Donohoe M, McGregor NR Hope D, Taylor WG, Watkins JA, Murdoch RN & Butt H (1996) Bioaccumulated chlorinated hydrocarbons and red/white blood cell parameters. Biochem Molec Med,58:77-84.
It is important to realise that many pesticide formulations usually contain less than 1% of the active ingredient. Most of the pesticides are lipophilic to facilitate entry into target organisms. In addition, they are delivered in appropriate solvent mixtures that usually contain dispersal agents.
Pesticides can therefore contain a complex cocktail of solvents and additives. These solvents can have substantial effects on exposed organisms, either by causing oxidative damage or by membrane disruption. They are rapidly excreted leaving no measurable trace, although they sometimes leave considerable cellular damage.
Pesticides in the body
Lipophilic pesticides such as DDT and HCB accumulate in the fatty tissues of the body. It should be remembered that every cell in the body is surrounded by a membrane of fatty structure. Limited exposure can therefore result in there being a very substantial distribution of pesticides around the body. The chemical and physical integrity of this membrane is vital to the proper function of cells.
These pesticides can interact with the membrane components, resulting in alterations to the membrane fluidity properties. They can also affect important membrane proteins.
The levels of these pesticides in the fatty tissues are usually several hundred times higher than observed in the serum. The serum appears to be in an equilibrium with the body loading of pesticides. Analyses of this fluid have been found to represent a good evaluation of the pesticide burden on the human body. © Bioscreen, CPRU, S Ashton and F Bartosy 1999 - 2001
Pesticide analyses
The pesticides DDE and HCB are routinely analysed by the CFS research team. These are lipophilic contaminants that can be absorbed by the body and stored in the fatty tissues for prolonged periods. Newcastle research has found that DDE, HCB, dieldrin and heptachlor epoxide were relatively common. These were the most frequently detected compounds in human samples from Sydney and Newcastle.
Group HCB DDE Total Organochlorines
Control 1.4 4.27 6.3
CFS 5.1 10.4 15.9
Above: A table showing a comparison of DDE and HCB levels found in control subjects and in CFS patients.
What do the DDE and HCB results indicate?
High levels of DDE are associated with increased red cell distribution width.
High HCB correlates with:
1. decreased percentage of eosinophils
2. decreased haemoglobin levels
Conclusion:
The changes in blood cell parameters do not necessarily need to be outside the "normal ranges" to have an influence on the health of the subject.
The above data indicates that elevated levels of organochlorine pesticides lead to substantial alterations in the functional capacity of blood cells to respond to external stimuli in CFS patients.
A summary of common pesticide types
DDT (dichlorodiphenyltrichloroethane): DDT was first synthesized in 1874 by Zeidler. It was first developed as an insecticide in 1939 by Dr. Paul Muller of the Geiger company in Switzerland. DDT was used extensively to control pests of importance to human health - house flies, mosquitoes, body lice and agricultural pests.
DDE (1,1-dichloro-2,2-bis(p-chlorphenyl) ethene):
DDE is a dehydrochlorinated product of DDT produced by metabolism of DDT in some organisms (including humans).
DDD (1,1-dichloro-2,2-bis(p-chlorophenyl)ethane):
DDD is produced by metabolism of DDT in some organisms.
HCB (hexachlorobenzene):
Hexachlorobenzene has been used extensively in Australia as a fungicide for the protection of grain in storage. It also occurs as a contaminant in the production of other chlorinated solvents (eg carbon tetrachloride) and in the production of nitroso-rubber for tyres. HCB can enter the environment from tyre residue. © Bioscreen, CPRU, S Ashton and F Bartosy 1999 - 2001
a-HCH, g-HCH, b-HCH (hexachlorocyclohexane):
Hexachlorocyclohexane was developed as a pesticide during World War II. The isomer -HCH was commonly known as "lindane" and has been used extensively in controlling insects of importance to public health.
Methoxychlor:
Methoxychlor is an insecticide in the same family of compounds as DDT. It is more rapidly dechlorinated than DDT.
Aldrin:
Aldrin is a cyclodiene insecticide which is chemically stable and highly lipophilic (attracted to fat cells). In the environment and in biological systems, it is rapidly converted to its epoxide, dieldrin. This is considered to be the primary toxic substance of aldrin. It has been used in the control of termites.
Dieldrin
Dieldrin is a cyclodiene insecticide that is chemically stable and highly lipophilic. It is one of the most persistent insecticides known. It has been used for the control of termites.
Endrin
Endrin is a stereo-isomer of dieldrin and has been used as an insecticide. It is more readily degraded in the environment than dieldrin and more rapidly metabolised by most organisms.
Chlordane
The commercial product is a mixture containing 60-75% of the pure compound and 25-40% of related compounds used. It is used to control termites.
Heptachlor
Heptachlor is an insecticide used in the control of termites. It has also been used in the cotton industry.
Heptachlor epoxide
Heptachlor epoxide is the biological conversion product of Heptachlor.
Heptachlor is an insecticide used against termites and for spraying cotton. The epoxide is more toxic than the parent heptachlor pesticide.
Endosulfan
The commercial product of Endosulfan is a mixture of 2 isomers, used as an insecticide and is very lipophilic.
Endosulfan sulfate
Endosulfan sulfate is the oxidation product of Endosulfan produced by metabolic processes in most organisms. © Bioscreen, CPRU, S Ashton and F Bartosy 1999 - 2001
PCBs (polychlorinated biphenyls)
Polychlorinated biphenyls have been produced under the name “Aroclor” for use in electrical components such as transformers and capacitors. They have been also used in printing inks, paints, dedusting agents, pesticides and other products.
PCBs are very stable chemicals and are extremely persistent in the environment. They occur in most human and animal adipose samples. They have been detected in milk, sediments and other matrices.
Further reading:
1) D.J. Ecobichon & R.M. Joy (1994) Pesticides and neurological diseases, second edition. CRC press, London ISBN 0-8493-4361-5
2) H. Aizawa (1982) Metabolic maps of pesticides. Academic Press New York. ISBN 0-12-046480-2
3) K. Short (1994) Quick poison, slow poison Envirobook ISBN0-85881-127-8 4) R. Carson (1962) Silent Spring. Penguin Books
5) G. de Jong (1991) Long term health effects of aldrin and dieldrin. Elsevier Science Publishers, Amsterdam (Toxicol Lett. Suppl.).
© CPRU and F Bartosy 1999
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