Rotenone

A recent study linking rotenone – a pesticide with a ‘natural’ image, commonly used in organic farming and gardening – to Parkinson’s disease, has increased demand for a level playing field in the safety assessment of pesticides. The current regulatory system, designed for synthetic agrochemicals, impedes research into, and registration of, least toxic, relatively benign pest control substances. 

What is rotenone
Rotenone is a naturally occurring chemical with insecticidal, acaricidal(1) (mite and spider-killing) and piscicidal (fish-killing) properties, obtained from the roots of several tropical and subtropical plant species belonging to the genus Lonchocarpus or Derris. It is a selective, non-specific insecticide, used in home gardens for insect control, for lice and tick control on pets, and for fish eradications as part of water body management(2). Both a contact and stomach poison to insects, it kills them slowly, but causes them to stop their feeding almost immediately(3). It exerts its toxic action by acting as a general inhibitor of cellular respiration(4).

Production
Rotenoids, the rotenone-related materials, have been used as crop insecticides since 1848, when they were applied to plants to control leaf-eating caterpillars. However, they have been used for centuries (at least since 1649) in South America to paralyse fish, causing them to surface(5). Derris root has long been used as a fish poison and its insecticidal properties were known to the Chinese well before it was isolated by E. Geoffrey in 1895(6). The use of the ground root of certain species of Derris was patented in 1912, since when it has been established that the active compounds are rotenoids, of which the main insecticide is rotenone(7).
    Rotenone is sold in dispersible powder, emulsifiable concentrate, and wettable powder formulations(8). In the UK, two professional products are registered: Devcol Liquid Derris, and Liquid Derris, and nine amateur products, including two wasp-killers. Another product marketed by pbi contains a mixture of rotenone and sulphur, both a fungicide and insecticide(9).
    Products containing rotenone are registered in Denmark, Ireland, UK, France, Spain, Italy(10). One product for fisheries management is also approved in Sweden, for restricted use(11).

Use
In the UK, rotenone products are approved for use against aphids on flowers, ornamentals, protected crops, soft fruit, top fruit, and vegetables, and against sawflies in gooseberries, and slug sawflies in pears and roses(12). 
    Very little rotenone is used in commercial fruit and vegetable production in the UK. The average annual total – all crops – is just three kilograms, used to treat 93 hectares. Since 1983, the minimum area treated annually was 22 hectares in 1985/86, and the maximum was 165 hectares in 1991(13). No data is collected for amateur usage, and total stocks for amateur products (in garden sheds and amongst wholesalers and retailers) are likely to be considerably greater than for professional use.
    Other target organisms of rotenone include maggots, bagworms, codling moths, Japanese beetles, leaf hoppers, Mexican bean beetles, cabbage worms, thrips, stinkbugs, flea beetles, and vegetable weevils(14).
    The UK Environment Agency, responsible for granting licences for the use of noxious substances for the taking or destroying of fish, under the Salmon and Freshwater Fisheries Act 1975, and rotenone is by far the most common chemical used for this purpose(15).

Use of rotenone in organic production
In organic production, the use of rotenone is permitted as an insecticide under European Union Regulation 2092/91, amended by 1488/97, Annex II (B)(16). In response to a recent study linking rotenone to Parkinson’s Disease(17), the UK Soil Association put a temporary ban on its use, pending further investigations.

Acute toxicity
Rotenone is classified by the World Health Organisation as a moderately hazardous, Class II(18). The LD50 for rats (the amount of the chemical lethal to one-half of experimental animals) is between 132 and 1,500 mg per kilogram(19). One factor in this wide variation may be the differences in the plant extracts used(20).
    The acute oral toxicity of rotenone is moderate for mammals, but there is a wide variation between species(21). It is less toxic for the mouse and hamster than for the rat; the pig seems to be especially sensitive. Recent studies have shown that in rats, rotenone is more toxic for females than males. It is highly irritating to the skin in rabbits(22), and to the eyes. In rats and dogs exposed to rotenone in dust form, the inhalation fatal dose was uniformly smaller than the oral fatal dose(23). 
    Rotenone is believed to be moderately toxic to humans with an oral lethal dose estimated from 300 to 500 mg/kg(24). A lowest lethal dose of 143 mg/kg has been cited in a child(25). Clinical experience seems to indicate that children, in particular, are rather sensitive to the acute effects of rotenone(26).
    Human fatalities are rare, perhaps because rotenone is usually sold in low concentrations (one to five per cent formulation), and because its irritating action causes prompt vomiting. If the dust particle size is very small, and can enter deep regions of the lungs, rotenone’s toxicity when inhaled may be increased. Acute local effects include conjunctivitis, dermatitis, sore throat, congestion, and vomiting. Inhalation of high doses can cause increased respiration followed by depression and convulsions(27). On the basis of rabbit studies, absorption through the intact skin is low(28).

Chronic effects
Studies on dogs at high doses produced adverse changes in blood chemistry(29). In dogs fed rotenone at 10 mg/kg per day for six months, weight loss and haematological effects were found. A No Observed Adverse Effect Level (NOAEL) of 0.4 mg/kg per day has been determined for rats (2-year study), and dogs (16-month study)(30).

Cancer
Published studies on the carcinogenic potential of rotenone are conflicting and inconclusive. Significant increases in mammary tumours have been reported in albino rats with intraperitoneal doses of 1.7 mg/kg/day for 42 days. But no evidence of carcinogenic activity was seen in hamsters at oral doses as high as 120 mg/kg/day for a period of 18 months(31).

Endocrine-disrupting effects
Rotenone is not included on any existing lists as an endocrine-disrupting pesticide(32).

Reproductive effects
Reproductive effects seem unlikely in humans at expected exposures. Foetotoxicity and failure of offspring are reported in guinea pigs at doses of 4.5 and 9.0 mg/kg/day for an unspecified period(33).

Teratogenic effects
Evidence for this is inconclusive. In one study, pregnant rats fed 5 mg/kg/day produced a significant number of young with skeletal deformities(34).

Neurotoxicity
The recent study administered rotenone by continuous infusion into the jugular vein of rats at dose levels of 1 to 12 mg/kg/body weight per day. The aim of the work was to develop a model for Parkinson’s disease, rather than study the toxicity of rotenone, and why this chemical was chosen is not clear. The optimal dose for producing Parkinson-like pathology was found to be 2 to 3 mg/kg/ body weight per day, clearly above the intravenous LD50(35). 
    A subsequent study, using much lower levels of chemicals, found that a combination of paraquat and maneb, but neither one alone, creates in mice the exact pattern of brain damage seen in Parkinson’s disease patients, and that older mice may be more sensitive to the combination than younger mice(36).

Consumer and occupational exposure
Estimates of operator exposures to rotenone products have been calculated. The Occupational Exposure Standard in air for rotenone is 5 mg/m3 (8 hours), 10 mg/m3 (10 minutes). For ‘talc’ (dust) it is 10 mg/m3 (8 hours), respirable 1 mg/m3 (8 hours)(37).

Fate in the environment
Rotenone is rapidly broken down in soil and water: its half-life in both is between one and three days(38). Nearly all its toxicity is lost in five to six days of spring sunlight, or two to three days of summer sunlight. It does not readily leach from soil and it is not expected to be a groundwater pollutant(39).

Water
Rotenone is highly toxic to fish: most values for the 96 hour LC50 (lethal concentration required to kill half the test organisms) for different fish species and for daphnids (water fleas) lie in the range of 0.02 to 0.2 mg/litre. If used as a piscicide, it may also cause a temporary decrease in numbers of other aquatic organisms(40).
    There is considerable controversy over the use of rotenone to kill non-game fish in water body management areas. One study found that the practice has a substantially harmful effect on biodiversity, in which several populations of the native fish showed negligible signs of recovering stocks, while populations of all exotic species are up(41).

Food residues
Rotenone is not included in regulatory food residue programmes, and therefore no data is available. 

Data gaps
The data base supporting the approval of rotenone is not to current requirements. NOAELs have not been determined for repeated exposures, no information is available on the extent of studies on its effect on the brain, and there is insufficient data on genotoxicity.

Conclusion
PAN UK believes that the same precautionary principle should be applied to all pesticides, and that no substance, however long-term its use, should be assumed to be safe without scientific assessment. The problems evident for rotenone – insufficient usage data, inconclusive studies, concern about unknown synergistic activity with other substances, and potential health hazards, are consistent with problems found with the majority of registered agrochemicals. (AC)

References
1. Extoxnet Pesticide Information Notebook Rotenone, revised 6/96.
2. Extoxnet, Ibid.
3. G Ware, Pesticides – theory and application, W H Freeman & Co, New York, 1978, 1983, page 53.
4. International Programme on Chemical Safety (IPCS), Rotenone Health and Safety Guide, Number 73.
5. G Ware, Op. cit. 3.
6. The Pesticide Manual, a world compendium, twelfth edition, Editor C D S Tomlin, British Crop Protection Council, 2000, page 828.
7. Pesticide Safety Directorate (PSD), pers. comm. 29 November 2001.
8. The Biopesticide Manual, first edition, Editor L G Copping, British Crop Protection Council, 1998, page 35.
9. PSD, Op. cit. 7.
10. European Union DG24, http://europa.eu.int/comm/food/fs/ph_ps/pro/eva/existing/exis02_en.pdf, page 9 of 12.
11. Margareta Persson, National Chemicals Inspectorate, pers comm., 10 October 2001.
12. The UK Pesticide Guide 2001, British Crop Protection Council & CABI publishing, page 506.
13. Department for the Environment, Food and Rural Affairs, Pesticide Usage Surveys in Great Britain, 1983/99.
14. IPCS, Op. cit.4.
15. PSD, Op.cit.7.
16. N Price, C Stopes Routes and barriers to the further exploitation of strategic research into biorational pesticides at CSL [Central Science Laboratory], 2001.
17. R Betarbet, T Sherer, G MacKenzie et al, Chronic systemic pesticide exposure reproduces features of Parkinson’s disease, Nature Neurosciences 3 (12), 1301-1306.
18. World Health Organisation(WHO), Recommended classification of pesticide by hazard, WHO/PCS/01.4 (2000-01).
19. WHO, Ibid.
20. IPCS, Op. cit. 4.
21. IPCS, Ibid.
22. IPCS, Op. cit. 4.
23. Extoxnet, Op. cit 1.
24. Extoxnet, Ibid.
25. IPCS),Op. cit. 4.
26. IPCS, Ibid.
27. Extoxnet, Op.cit. 1.
28. IPCS, Op. cit. 4.
29. Extoxnet, Op. cit. 1.
30. IPCS, Op. cit. 4.
31. Extoxnet, Op. cit. 1.
32. List of Lists, Pesticide Action Network UK, November 2001.
33. Extoxnet, Op. cit.1.
34. Extoxnet, Ibid.
35. R Betarbet, Op.cit. 17.
36. D Cory-Slechta et al, University of Rochester School of Medicine and Dentistry, Journal of Neuroscience, December 2000, reported in Environment News Service, 3 January 2001. 
37. Vitax Safety Data Sheet for Derris dust, revised October 1998.
38. PSD, Op.cit. 7.
39. Extoxnet, Op.cit.1.
40. IPCS, Op.cit. 4.
41. Long term effect of rotenone treatment on the fish community of Big Chico Creek, California, pmaslin@oavax.csuchicho.edu

[This article first appeared in Pesticides News No. 54, December 2001, pages 20-21]