Carbaryl re-assessed

Carbaryl is widely used as an insecticide with acute toxic effects which are well known. Recent data on its carcinogenic potential has indicated the need for further research, and has prompted a revision of safety controls governing its use.

Description
Carbaryl, a carbamate insecticide, is a cholinesterase inhibitor, and can also act as a plant growth regulator. It is used to kill a range of chewing and sucking insects on over 120 agricultural crops. In UK agriculture, it is mostly used against caterpillar pests on apples. Internationally it is used on citrus fruit, mangoes, bananas, strawberries, nuts, vines, olives, okra, cucurbits, peanuts, soya beans, cotton, rice, tobacco, cereals, beet, maize, sorghum, alfalfa, potatoes, ornamentals and forestry. Carbaryl has also been used against earthworms in turf and amenity grass. Carbaryl is used against ectoparasites of humans and animals, including against head lice on children(1,2).    
Carbaryl was introduced by Union Carbide (whose pesticide interests were taken over by now Rhône-Poulenc after the Bhopal gas disaster) in the early 1960s. Principal producers are: Rhône-Poulenc; Drexel Chemical Company; Jin Hung; and Makhteshim-Agan. Carbaryl is processed by more than 290 formulators in over 1,500 different products(3,4).
    In 1992 in the UK, it was the seventh most used active ingredient by weight on top fruit and was used on over 15,000 treated hectares on apples, pears and plums(5).

Health effects
Acute toxicity
Carbaryl is classified by the World Health Organisation (WHO) as 'moderately hazardous' (Class II)(6). The acute toxicity varies considerably according to species and formulation. Estimates for the oral LD50 of the rat range from 200 to 850 mg/kg. Cats are sensitive to carbaryl with an LD50 of 150 mg/kg, whilst pigs and monkeys are less susceptible having an LD50 greater than 1,000 mg/kg(7).
    Carbaryl can produce adverse effects in humans by skin contact, inhalation or ingestion. Its main mode of action involves the inhibition of the nerve enzyme cholinesterase and consequential disruption of the nervous system. The symptoms of acute toxicity are similar to other carbamates. Direct contact with the skin or eyes with moderate levels can cause burns. Inhalation or ingestion at high doses can be toxic to the nervous and respiratory systems resulting in nausea, stomach cramps, diarrhoea and excessive salivation, sweating, blurring of vision, lack of co-ordination and convulsions(8).
    The US Environmental Protection Agency carried out a review of carbaryl-related poisoning between 1966 and 1980. During this period, 193 cases involving solely carbaryl and 144 cases which included carbaryl as one of the active ingredients, were assessed(9).
    Workers have the greatest potential for exposure through inhalation or dermal absorption. The highest risk of exposure for the general public is through residues in food(10,11).

Manufacturing
On 3 December 1984 a gas leak containing methyl isocyanate (MIC) escaped from a Union Carbide factory in Bhopal, India. The MIC, an intermediate product used to make carbaryl, killed between 2,500 and 5,000 and injured about 200,000 (see PN26). A similar but smaller incident happened a year later at Union Carbide's plant in West Virginia which also produced carbaryl and aldicarb. In this case 135 people were injured(12).

Carcinogenicity
In 1987 carbaryl assessment by the International Agency for Research on Cancer (IARC) concluded that there were no data on cancer in humans and that the evidence of carcinogenicity in experimental animals was inadequate. This was reinforced in 1994 by a WHO Task Group report which concluded that most of the numerous cancer studies involving rats and mice were old and did not meet contemporary standards. The Group was aware that a pesticide company was carrying out new studies. Although they had not seen all the results, the Group was informed that these studies indicated significant increases in tumours at the highest dose in both rat and mice species. One of the main recommendations from the WHO report included a request that carcinogenicity studies meeting modern standards should be conducted(13).
    In the UK, in November 1995, new company data indicated carbaryl could cause cancer in humans, although the research is not yet in the public domain. The studies were assessed by the Committee on Carcinogenicity and the Advisory Committee on Pesticides, which, in reporting to the government, concluded that it would be"prudent to consider carbaryl as a potential human carcinogen"(14). The principal government response concerned the use of carbaryl against head lice in children. As a result, medicinal uses will only be available on prescription (see PN30 p.4).

Mutagenicity
Studies indicate that carbaryl is slightly mutagenic(15,16). A WHO assessment concludes from available data that carbaryl does not pose a threat of inducing genetic changes in humans(17). However, carbaryl can react with nitrite under certain conditions to form N-nitrosocarbaryl. This chemical is highly mutagenic at low levels in laboratory test systems. This may be of concern because nitrite can be found in food additives and human saliva which can react with carbaryl in the stomach to form N-nitrosocarbaryl(18).

Reproductive toxicity
The US EPA has concluded that carbaryl does not pose a teratogenic risk to humans(19). However, it is considered to have endocrine disruptor effects(20).

Environmental effects
Carbaryl is lethal to many non-target species. The destruction of honeybee populations in sprayed areas is sometimes a problem. The insecticidal properties of carbaryl last for about 3-10 days. Degradation of carbaryl in the soil is mostly due to sunlight and bacterial action. It is bound by organic matter and can be transported by run-off. Carbaryl has a half-life of 7 days in aerobic soil and 28 days in anaerobic soil. In pond water, carbaryl has a half life of 1 to 32 days and it has been detected in groundwater in three separate sites in California(21).

Residues
Residues of carbaryl are regularly detected in tests on fruit and vegetables in the UK. In the latest report covering the period 1994, residues were found in dessert and cooking apples, grapefruit, ready prepared fruit-based baby food and lettuce. In none of these cases were the maximum residues limits exceeded(22). Carbaryl is the tenth most commonly found pesticide in a 1994 total diet survey carried out by the US Food and Drug Administration(23).

Recommendations for use
Because of an announcement on 7 November by the UK government concerning its carcinogenic affects, carbaryl will no longer be approved for non-professional uses; will be available for medical uses only by prescription; and professional use is subject to restrictions designed to limit exposure. These are:

• applications must only be made using a vehicle with a closed cab;
• a low level induction bowl or closed systems must be used for transferring the product to the spray tank;
• coverall apron and gloves must be worn when handling the concentrate, (previously a face shield had also to be worn);
• coverall must be worn during application;
• coverall must be worn when handling contaminated surfaces;
• the latest time of treatment of top fruit is three weeks before harvest (previously it was seven days)(24).

Conclusion
At the end of 1995, the UK government's position on carbaryl changed, carbaryl is now considered to be a potential human carcinogen. Four main issues arise as a result:

• Given the health and safety and resistance concerns about alternative pesticide active ingredients in head lice preparations malathion, permethrin and, less frequently lindane - there should be a review of all head lice preparations containing pesticides.
• There remains considerable risk to agricultural and horticultural uses of carbaryl, as cited above. There should therefore be a label warning to indicate carbaryl is, in the view of the Advisory Committee on Pesticides, 'a potential human carcinogen'.
• Rodent carcinogenicity data, submitted by the manufacturer, is not in the public domain. A government full evaluation document on carbaryl should be made available promptly, particularly covering agricultural and horticultural use.
• The stringent protective clothing requirements imposed must call into question whether the safe use of carbaryl is possible in developing countries.

References
1. Tomlin, Clive (Ed), The Pesticide Manual, Tenth edition, British Crop Protection Council (BCPC), Royal Society of Chemistry, UK, 1994, p149.
2. Whitehead, R. (Ed), The UK Pesticide Guide 1995, BCPC and CAB International, p190.
3. Carbaryl, Environmental Health Criteria No. 153, International Programme on Chemical Safety, UNEP, WHO, ILO, Geneva, 1993, p13.
4. Op. cit. 1.
5. Orchards and Fruit Stores in Great Britain 1992, Pesticide Usage Survey Group 115, MAFF, 1994.
6. The WHO recommended classification of pesticides by hazard and guidelines to classification 1994-1995.
7. Op. cit. 1.
8. Data Sheet on carbaryl, Extoxnet, Extension Toxicology Network, Oregon State University, US.
9. Op. cit. 3 p9.
10. Baron, R., Carbamate Insecticides, In Handbook of Pesticide Toxicology, Vol. 3, W.J. Hayyes and E.R. Lawes (Eds.), 1991, Academic Press, US.
11. Op. cit. 3 p14.
12. Journal of Pesticide Reform, Summer 1993, Vol 13, No.1, p33.
13. Op. cit. 3. p22.
14. Carbaryl, Joint announcement of MAFF's Pesticide Safety Directorate and Health and Safety Directorate, 7 November 1995.
15. Seibert, D., and Eisenbrand, G., Mutation Research, 1974, 80:1-64.
16. National Library of Medicine, Hazardous Substances Databank, Carbaryl, February 4 1992.
17. Op. cit. 3 p17.
18. Op. cit. 8.
19. Ibid.
20. Chemically induced alterations in sexual and functional development: The wildlife/human collection, eds. T. Colborn and C Clement, Princeton Scientific Publishing, Princeton, NJ, 1992.
21. Op. cit. 8.
22. Annual report of the Working Party on Pesticide Residues 1994, HMSO, London, UK, 154pp.
23. Pesticide Program, Residue Monitoring, 1994, Food and Drug Administration, US, p15.
24. Op. cit. 14.

[This article first appeared in Pesticides News No.31, March 1996, p20-21]