Chlorpyrifos

Chlorpyrifos was originally marketed in the US in the 1960s and is now one of the word's leading insecticides. More recently concerns about related health effects have led to restrictions on its use.

What is chlorpyrifos?
Chlorpyrifos is one of about 100 organophosphate (OP) insecticides on the market today. It is used to kill insect pests by disrupting their nervous system. Chlorpyrifos has an advantage over other products in that it is effective against a wide range of plant-eating insect pests.

Production
Chlorpyrifos (trade name Dursban, Lorsban and others) is primarily produced by the US multinational DowElanco. Other manufacturers are Aimco, Agriphar, Excel, Ficom, Gharda, Lupin, Montari (all India), Frunol (Germany), Jin Hung (South Korea), Point Enterprises (Switzerland) Luxembourg and Makhteshim-Agan, (both Israel). DowElanco protects the compound from generic competition vigorously and in 1995 received compensation form Micro Flo who, DowElanco claimed, had used DowElanco data to obtain US registration without paying for the data(1).

Uses and usage
Chlorpyrifos is the world's leading insecticide in volume terms(2). It was first reported in the scientific literature in 1966, and was originally developed by Dow Chemical Co. (now Dow Elanco)(3). This OP is used extensively in the US, in agriculture, and both inside and outside the home environment. In agriculture, it is used primarily on corn (maize), alfalfa and cotton.
    Figures on usage are not generally available. In the US, the Journal of Pesticide Reform indicated that during the mid-1990s, 9-12 million pounds (4-5.5 million kg) were used annually in non-agricultural situations in over 17% of households. Agricultural usage estimates vary even more with annual application anywhere between 10 and 21 million pounds (4.5-10 million kg)(4).
    In the UK, chlorpyrifos is more commonly used in agriculture, although no really accurate figures are available for use in the home.
    During 1997 about 100,000 kg were used on about 50 different agricultural crops. Those most heavily dosed in descending order were grassland, wheat, spring barley, desert apples and culinary apples(5). Chlorpyrifos is registered for household use against ants and wasps, and by professional users for use in food storage areas against insects(60.

Acute toxicity
The acute oral LD50 (the dose required to kill half of a population of laboratory test animals) for chlorpyrifos is between 135-165 mg/kg for rats(7). It is classified by the World Health Organisation as a Class II, 'moderately hazardous' pesticide(8).
    Chlorpyrifos and other insecticide OPs are inhibitors of anticholinesterase (ACh-ase), an enzyme vital to the nervous systems of animals and humans. The transmission of impulses across certain nerve junctions (including, in humans, those of the autonomic nervous system) involves the release of a transmitter chemical, acetylcholine (ACh). The stimulant effect on ACh is rapidly cancelled by ACh-ase activity. The inhibiting effect of OPs on ACh-ase results in sustained high levels of ACh with consequent serious and widespread disruption of nervous activity.
    Chlorpyrifos is one of the leading causes of acute insecticide poisoning in the US, according to the US Environmental Protection Agency (EPA)(9).
    Symptoms of acute chlorpyrifos poisoning in humans include headache, nausea, dizziness, muscle twitching, weakness, increased sweating and salivation, and occur when cholinesterase activity has been reduced by about 50%. Unconsciousness, convulsions, and death can result with sufficient exposure. These symptoms are common to all organophosphate insecticides with delayed symptoms one to four weeks after exposure of numbness, tingling, weakness and cramping in the lower limbs which can progress into paralysis(10) (see also PN34 fact sheet on OPs).   
    Effects on the central nervous system may include confusion, drowsiness, depression, difficulty concentrating, slurred speech, insomnia, nightmares, and a form of toxic psychosis resulting in bizarre behaviour(11).
    Chlorpyrifos poses a risk of serious damage to eyes, and is irritating to skin(12). Poisoning via the skin can easily be misdiagnosed suggesting some cases of occupational exposure are missed(13). The dermal LD50 for rabbits is about 2,000 mg/kg(14).

Chronic effects
The adverse effects of OPs are currently the subject of much debate in the UK. A recent government report concluded that their potential to cause ill health following long-term low-level exposure remains unknown and subject to controversy(15).
    Repeat or prolonged exposure to chlorpyrifos may result in the same effects as acute exposure, including the delayed symptoms. Other effects reported on workers repeatedly exposed include impaired memory and concentration, disorientation, severe depression, irritability, confusion, headache, speech difficulties, delayed reaction times, nightmares, sleepwalking and drowsiness or insomnia. An influenza-like condition with headache, nausea, weakness, loss of appetite and malaise has also been reported(16).
    In 1996, the Multiple Chemical Sensitivity Referral and Resources in the US cited cases of over 450 adults and children who were poisoned by the pesticide in their home or workplace. Their most common symptoms were chronic headaches, nausea and vomiting, breathing difficulties, vision problems, neuromuscular pains and multiple chemical sensitivity(17).
    In 1997, the US EPA announced a Risk Reduction Plan for Chlorpyrifos which included restrictions on its use because of a number of alleged ill-health effects cases. They included 22 reports of alleged nervous system disorders and 35 cases that alleged sensitivity to the chemical(18) (see also Restriction below).

Birth defects
According to the US EPA, it is not known whether chlorpyrifos can affect reproduction or cause birth defects in people, although these potential problems have been the subject of much debate(19). In 1996, a national coalition of US environmentalists(20) called on the EPA to issue emergency regulations restricting the use of Dursban because of concerns that it could cause birth defects.
    An independent scientific study reported four cases of serious and disabling birth defects seen in children whose mothers were exposed to Dursban during the first three months of their pregnancy. These children have deformed heads, faces, eyes and genitals - and require constant care. The report concluded that "exposure to Dursban is consistent with a common teratogenic (birth defect) agent. The production of similar defects in animals exposed to Dursban and its components supports this teratogenic connection(21)."

Cancer
The US EPA classification indicates that chlorpyrifos shows no evidence of carcinogenicity(22). However, according to the Journal of Pesticide Reform, xylenes, used as solvents in some chlorpyrifos-containing products, have caused increased rates of leukemia among exposed workers. Xylenes may also be co-carcinogens and increase the number of skin cancers caused by other carcinogens in laboratory animals(23).

Effects on the immune system
Recent research has identified immune system abnormalities in individuals following chlorpyrifos exposure. Higher than usual frequencies of allergies and sensitivities to antibiotics together with atypical abundances of certain types of lymphocytes (decreases in T cells and increases in CD26 cells) were found in patients one to five years after chlorpyrifos exposure. Increased expression of CD26 cells is associated with autoimmunity, where an individual's immune system acts against itself, rather than against infections(24).

Children
Recent US research showed that if a child played in his/her home a week after chlorpyrifos application, there was a danger that he/she would be overexposed to chlorpyrifos. The researchers were still finding chlorpyrifos residues on toys two weeks after application(25). Based on the findings of this and other research, the estimated chlorpyrifos exposure levels from indoor spraying for children are about 21-119 times above the US-recommended reference dose of 3 mg/kg/day from all sources(26).

Food residues
A national survey of pesticides and their metabolites in the US found that the primary chlorpyrifos breakdown product, 3,5,6-trichloro-2-pyridinol was the second most commonly detected chemical in food(27).
    Chlorpyrifos is regularly detected in UK fruit and vegetables. The latest report for 1997 shows that one sample out of 15 of Spanish celery was detected at 0.06 mg/kg which exceeded the maximum residue limit of 0.05 mg/kg(28).

Environmental fate
Chlorpyrifos is relatively non-persistent in the environment. However, aquatic invertebrates, particularly crustaceans and insect larvae are sensitive to exposure. The LC50s for these species are generally less than 0.1 mg/litre(29).

Restrictions on use
In 1997, the EPA, in conjunction with manufacturers, designed policies to reduce exposure in the home, especially to children. They agreed to eliminate chlorpyrifos concentrates that require mixing, limit household consumer use to ready-to-use products, and prohibited use in inappropriate areas (toys, curtains and furnituture)(30).

Conclusion
In common with other OPs, chlorpyrifos usage has raised a number of concerns during the 1990s. Most of the examples of ill-health problems originate from the US. However chlorpyrifos is used widely throughout the world, and it is likely that many US exposure conditions can be related to the rest of the world.

References
1. Agrow's Top Twenty Five, PJB Publications,1997.
2. Ibid.
3. CDS Tomlin, The Pesticide Manual, BCPC, 1997, p235-237.
4. Caroline Cox, Chlorpyrifos, Part 1: Toxicology, Journal of Pesticide Reform, 1994, Vol. 14, No. 4, p15.
5. Pers. Comm., Miles Thomas, Head, Pesticide Survey Group, Central Science Laboratory, Sand Hutton, York, 1998.
6. OPs and Sheep Dips, the Pesticides Trust [now PAN UK], 1998.
7. Op. cit 3.
8. The WHO Recommended Classification of Pesticides by Hazard 1996-1997, International Programme on Chemical Safety, WHO/IPCS/96.3.
9. Review of Chlorpyrifos Poisoning Data, US EPA, 1995.
10. Extension Toxicology Network (EXTOXNET) Chlorpyrifos, Oregan State University, US, 1993.
11. Op. cit. 9.
12. R. Whitehead, The UK Pesticide Guide, CAB International/BCPC, 1998.
13. Op. cit.9.
14. Op. cit. 3.
15. Official Group on OPs Report to Ministers, MAFF publications, 1998, p23.
16. Op. cit. 10.
17. Researchers Link Common Household Insecticide with Serious Birth Defects and MCS, MCS Referal and Resources, press release, 20 November 1996.
18. Risk Reduction Plan for Chlorpyrifos, US EPA, press release, June 1997.
19. Chlorpyrifos, Agency for Toxic Substances and Disease Registry, US Department of Health and Human Services.
20. Op. cit. 17.
21. Janette Sherman, Chlorpyrifos (Dursban) Associated Birth Defects, International Journal of Occupational Medicine and Toxicology, 1995, Vol. 4., No. 4:417-431.
22. List of chemicals evaluated for carcinogenic potential, US EPA, 1994.
23. Op. cit. 4, p18-19.
24. JD Thrasher R, Madison et. al., Immunologic abnormalities in humans exposed to chlorpyrifos, Archives of Environmental Health, 1994, Vol. 14, p18. Also op. cit 4.
25. S. Gurunathan, et. al., Accumulation of Chlorpyrifos on Residual Surfaces and Toys Accessible to Children, Environmental Health Perspectives, 1998, Vol. 106:9-16.
26. Devra Lee Davis and Karin Ahmed, Exposures for Indoor Spraying of Chlorpyrifos Pose Greater Health Risks to Children than Currently Estimated, Environmental Health Perspectives, Vol. 106:299-301.
27. Caroline Cox, Chlorpyrifos, Part 2: Human Exposure, Journal of Pesticide Reform, 1994, Vol.15, No1, p14.
28. Annual Report of the Working Party on Pesticide Residues, 1997, MAFF Publications, 1998.
29. Mace Barron and Kent Woodburn, Ecotoxicology of Chlorpyrifos, Reviews of Environmental Contamination and Toxicology, 1995, Vol. 144.
30. Op. cit 18.

[This article first appeared in Pesticides News No.41, September 1998, p18-19]