Cypermethrin - a synthetic pyrethroid

Cypermethrin has become one of the most important insecticides in wide-scale use. It has been said that "no pesticide is perfect, but the pyrethroids come close."(1)  Is this assessment accurate?

Description
Cypermethrin acts as a stomach and contact insecticide. It has wide uses in cotton, cereals, vegetables and fruit, for food storage, in public health and in animal husbandry. Its structure is based on pyrethrum, a natural insecticide which is contained in chrysanthemum flowers, but it has a higher biological activity and is more stable than its natural model. It was synthesised in 1974 and first marketed in 1977, by Shell (which has since sold their pesticide business to American Cyanamid.
    In 1988, pyrethroids amounted to 40% of the sales for insecticides for cotton treatment in the world (cypermethrin 8%)(2), and cypermethrin is one of the most important insecticides for cereals and vegetables in the UK. There has been a dramatic increase in the use of cypermethrin for arable crops in the UK: from approximately 216,000 ha in 1988 to 1,582,000 ha sprayed in 1992, falling back to 863,000 ha in 1994(3). It is also used for impregnation of mosquito bed nets to prevent malaria, and extensively for indoor pests. As many patents for pyrethroids expire between 1993 and 1996, the market looks set to open up dramatically(4). 

Health issues
Acute toxicity
Cypermethrin is classified by the World Health Organisation (WHO) as 'moderately hazardous' (Class II)(5). It interacts with the sodium channels in nerve cells through which sodium enters the cell in order to transmit a nerve signal. These channels can remain open for up to seconds, compared to the normal period of a few milliseconds, after a signal has been transmitted. Cypermethrin also interferes with other receptors in the nervous system. The effect is that of long-lasting trains of repetitive impulses in sense organs.
    Symptoms of poisoning include abnormal facial sensations, dizziness, headache, nausea, anorexia and fatigue, vomiting and increased stomach secretion. Cypermethrin is also a skin and eye irritant. Normally, symptoms should disappear after some days but severely exposed patients additionally may suffer from muscular twitching, comata and convulsive attacks. In such cases, symptoms may persist for some weeks.
    Most cases of pyrethroid poisoning have been reported in China(6)  (nearly 600 between 1983 and 1988, of which 45 involved cypermethrin). They occur among farmers, mostly after misuse. Recently, poisonings have as well been reported after indoor use of pyrethroids in Germany among pest controllers and private users (see PN 29 p.3).

Chronic toxicity
Chronic symptoms after exposure to pyrethroids have now been reported(7). Symptoms include brain and locomotory disorders, polyneuropathy and immuno-suppression, and resemble the multiple chemical sensitivity syndrome (MCS).

Carcinogenicity
Opinions differ as to whether cypermethrin is a carcinogen or not. Cypermethrin is classified by the US EPA as a weak category C oncogen - a possible human carcinogen with limited evidence of carcinogenicity in animals but no evidence of carcinogenicity in humans: it produced benign lung adenomas (tumours) at the highest dose level in female mice and has potential for liver carcinogenicity in rodents. However, the view of WHO is that as there was no evidence of carcinogenicity in male mice and as the results of mutagenic studies have been mainly negative "it is concluded that there is no evidence for the carcinogenic potential of cypermethrin."(8) 

Mutagenicity
Cypermethrin was found to be genotoxic in mouse spleen and bone marrow(9)  but other tests have been negative.

Immune suppression
Testing on rats has suggested that pyrethroids in general may have an immuno-suppressive effect. WHO concludes that "more attention should be paid to this aspect, but at present, no opinion can be given about its relevance in the extrapolation of these data for man."(10)

Reproductive toxicity
When administered to pregnant and nursing rats, cypermethrin may lead to a functional delay in the brain maturation of the pups. The toxicity to young rats is higher the younger they are, also because the pathway for degrading cypermethrin is not readily developed in young rats.

Environmental effects
The pyrethroids are widely used because of their general low toxicity to birds and mammals. However, they are highly toxic to aquatic organisms and fish as well as to bees - with the same mode of action in each organism. The LC50 values for small fish and other aquatic organisms typically lie below 1 µg/l, and the LD50 value for bees is 0.03 - 0.12 µg/kg. For use with conventional hydraulic sprayers, buffer zones of 16-24 m are needed to reduce mortality of butterflies in the surroundings(11).
    Although the direct acute toxicity towards birds is small, they are affected via the food chain: in a treated wood, only 20% of the nestlings of the blue tit, a beneficial bird, survived(12). Other beneficial organisms that can be affected by cypermethrin include beetles, spiders and centipedes living on the soil and predatory mites. Populations are reduced to 20% in some experiments, but recover after some weeks.
    Despite earlier findings, the microbial population of soil is affected by cyper-methrin: the ammonification and nitrification in treated soils is enhanced, a sign of the environmental impact of cypermethrin(13). 
    Once applied, cypermethrin is bound strongly by soil components and is therefore not likely to enter ground water. Cypermethrin is not persistent in soil and quickly degrades to less toxic products (with a half life of 2 to 4 weeks). In contrast, cypermethrin persists in treated wood for up to seven months in the soil and on bark(14) .

Residues
The relatively rapid degradation of cypermethrin means that it is not generally found as a residue in food. Residues have been found in UK imported lettuce, where one sample out of 30 exceeded the UK MRL(15) , and in Pakistan, where the maximum residue level (MRL) was exceeded about 30 fold in turnip and okra (see PN p.19).
    After indoor use, cypermethrin residues may be found in dust and carpets with a concentration up to 4 mg/kg(16). The concentration in the air after an indoor treatment increases rapidly, but can then stay relatively constant for months at values for which pyrethroids can cause adverse health effects (3-8 µg/m3) (17,18).

Recommendations for use
Safety precautions for handling include: avoid contact with skin and eyes; use PVC gloves, goggles, respirator mask, protective overalls and footwear; and keep children and pets away from areas being treated. In case of accidents, the following rules apply:

• skin contact: remove contaminated clothes. Wash exposed areas with plenty of mild soap and water
• eye contact: flush with clean water for 15 min. Seek medical aid
• inhalation: keep subject under observation
• ingestion: when the patient is conscious, provoke vomiting (by pharyngeal stimulation). Seek medical aid

Following investigations of a great number of poisonings in China, F. He gives the following recommendations for the use of pyrethroids(19):
    "Workers with skin diseases, central and peripheral nervous diseases should not be exposed to pyrethroids.
    "Appearance of abnormal facial sensations during pyrethroid exposure indicates the necessity of reducing exposure (improved work practices, enhanced personal protection, improvement of ventilation, etc.).
    "Exposure to pyrethroids should be ceased if the exposed subjects, in addition to having abnormal facial sensations, develop systemic symptoms such as headache, dizziness, nausea and fatigue. These subjects should not be allowed for readmission to work with pyrethroid exposure until all above-mentioned symptoms have disappeared."

Synthetic pyrethroids
Resistance
As the pyrethroids are chemically relatively similar, a pest species resistant to one member of the pyrethroid family is often resistant to another or even to all types(20).  Replacing one pyrethroid by another may not therefore be appropriate when resistance occurs. Resistance against cypermethrin is reported widely for the tobacco budworm (one of the most important pests on many crops in the US and Mexico)(21). Some Heliothis species, the most serious pests on cotton, also developed resistance against pyrethroids, which led to severe yield losses worldwide(22). The onset of resistance is frequently accompanied by increased doses of toxic pesticides, gradual loss of pest control and consequent loss of famers' income and increase in pesticide hazard.

Possible effects on the reproductive system
One report on an epidemic of gynecomastia (enlargement of the breast among males) among Haitian refugees(23) considers exposure to the synthetic pyrethroid phenothrin may be the cause. Experimental evidence suggests the pyrethroid molecule may bind to sex hormone binding globulin (SHBG) in vitro. Chronic exposure to pyrethroids may result in disturbances in hormonal effects relating to androgen action. Pyrethrins and in particular bioallethrin interact strongly with SHBG at concentrations of 40 mg/kg. The authors advise protection "from any form of contact or ingestion of the pyrethroids in order to prevent any undesirable effects on the human reproductive system until additional toxicological and endocrine studies can be conducted in vivo."

Cancer
A new study links leukaemia and lymphoid cancer with pyrethroid insecticides - although they showed only very little carcinogenic activity in previous toxicological studies. More than 20% of the leukaemia cases (women) and 10% (men) are linked with pyrethroid exposures (see PN28 p.27).

Problems with IPM
Synthetic pyrethroids will control a wide range of insects in a wide range of crops. Unfortunately, this broad-spectrum nature can adversely affect many non-target beneficials, distrupting, in particular, integrated pest management (IPM) programmes(24).

Indoor use
Recent research from Germany drew attention to potential health hazards of the use of synthetic pyrethroids in the home (see PN29 p. 3). There are also concerns raised by research about the development of resistance in indoor pest control(25).
    In a petition of May this year (Drucksache 13/1478, 23 May 1995) the parliamentary group of the German SPD called upon the Federal Government to prohibit the use of pyrethroids in textiles and the interior and, in addition, to give advice on non-toxic methods of fighting pests.

Conclusions
New studies show that the health effects of cypermethrin and pyrethroids in general may be more severe than previous toxicological evaluations suggest. Further studies on carcinogenicity and chronic toxicity are required.

References
1. Leahey, J.P. (ed.), The Pyrethroid Insecticides, Taylor & Francis, London, 1985.
2. Cotton: the crop and its agrochemicals market, Allan Woodburn Assoc. Ltd., Edinburgh, 1995.
3. Pesticide Usage Survey Reports 78 and 127, Ministry of Agriculture, Fisheries and Food, London 1990 and 1995 respectively.
4. Agrow 212, 1994, p. 17.
5. WHO Recommended Classification of Pesticides by Hazard 1994-95, WHO, Geneva.
6. He,F., Synthetic pyrethroids, Toxicol., 1994, 91, p. 43.
7. Müller-Mohnssen, H., Über eine Methode zur Früherkennung neurotoxischer Erkrankungen (am Beispiel der Pyrethroidintoxikation, Ges.Wes., 1995, 57, p. 214.
8. Cypermethrin. Environmental Health Criteria 82, WHO, Geneva, 1989.
9. Amer, S.M. et al., Induction of chromosomal aberrations and sister chromatid exchange in vivo and in vitro by the insecticide cypermethrin, J. Appl. Tox.,1993, 13:5, p. 341.
10. Cypermethrin. Environmental health Criteria 82, WHO, Geneva, 1989.
11. Davis, B.N.K. et al., Insecticide drift from ground-based, hydraulic spraying of peas and brussels sprouts - bioassays for determining buffer zones, Agricult. Ecosyst. Environm., 1993, 43:2, p. 93.
12. Pascual, J.A., Peris, S.J., Effects of forest spraying with two application rates of cypermethrin on food supply and on breeding successes of the blue tit (parus caeruleus), Env. Toxiol. Chem., 1992, 11, p1271.
13. Rangaswamy,V., Venkateswarlu,K., Ammonificarion and nitrification in soils, and nitrogen fixation by azospirillium sp. as influenced by cypermethrin and fenvalerate, Agricult. Ecosyst. Environment, 1993, 45, p. 311-317.
14. Class,T.J., Environmental analysis of cypermethrin and its degradation products after forestry applications, Int. J. Environm. Anal. Chem., 1992, 49:4, p. 189.
15. Annual Report of the Working Party on Pesticide Residues 1994, HMSO, London 1995.
16. Walker, G. et al., Anreicherung von Bioziden in Innenräumen am Beispiel der Pyrethroide, Zbl. Hyg., 1994, 195, p. 450
17. Wright, C.G. et al., Cypermethrin in the ambient air and on surfaces of rooms treated for cockroaches, Bull. Env. Cont. Tox., 1993,51:3, p. 356.
18. Op. cit. 5.
19. Op. cit. 6.
20. Beugnet, F. et al., Tick resistance to pyrethroids in New Caledonia, Vet. Parasit.,1995, 56:4, p.325.
21. Martinez-Carrillo, J.L., et al., Responses of populations of the tobacco budworm (Lepidoptera:Noctuidae) from Northwest Mexico to pyrethroids.
22. Rosier, M.J., Cotton, Pesticide Outlook, 1990,1:5, p.19.
23. Eil, C., and Nisula, B.N., The Binding Properties of Pyrethroids to Human Skin Fibroblast Androgen Receptors and To Sex Hormone Binding globulin. J. Steroid Biochem, 1990, 35:3-4, pp. 409-14.
24. CIRAD database on pesticides and the environment, 1994.
25. Chapman, P.A., Webb, D.P., and Walker, S.J., The Potential of some newer photostable pyrethroids to select for resistance in the housefly Musca domestica. Bull. Entom. Res. 1993, pp. 517-21.

[This article first appeared in Pesticides News No.30, December 1995, p20-21]