Lindane

A chemical of the past persists in the future

Introduction
Lindane is an organochlorine insecticide that is still in relatively widespread use in developed nations as well as in the third world. Many other organochlorines which over the years have been linked to major health and environmental problems have been banned or are no longer used. Included in this catalogue are aldrin, dieldrin and endrin which have virtually disappeared, and DDT, heptachlor and toxaphene which have been banned in many countries but are still used quite extensively particularly in some developing countries.
    Lindane is also known as gamma-HCH since it is made up of at least 99% of the gamma­isomer of hexachlorocyclohexane (HCH). 'Technical HCH' can include varying proportions of alpha, beta, delta and epsilon HCH isomers which have been shown to have serious short and long term health effects.
    While gamma-HCH and other isomers of HCH were isolated in the 19th century (lindane was first prepared by Faraday in 1825), the insecticidal properties of lindane were not recognised until the early 1940s; about the same time as DDT was developed. Lindane has been in use as an insecticide for nearly 50 years.
    The organochlorines in general, and lindane in particular, are characterised by their broad spectrum insecticidal activity, long persistence in the environment, and their tendency to bio-accumulate along food chains.
    The mode of action of lindane on insects is generally as a stomach poison with some fumigant action, that is it kills insects that ingest it or inhale its vapour. It kills insects by stimulating the central nervous system causing trembling, hyperexcitation, loss of coordination, paralysis, and eventually death. Although lindane acts on the nervous system of insects it is not a cholinesterase inhibitor as are the organophosphate insecticides, which were originally developed as nerve gases. The physiological mode of action of lindane is not well understood - it just works well as an insecticide.

Lindane as a global issue
Lindane is manufactured in India, US, Japan, and China. The raw active ingredient is formulated into hundreds of commercial products around the world. Although it has been banned for all uses in 7 countries, severely restricted in another four. Under the Prior Informed Consent (PIC) procedures, a further 23 countries have prohibited its import.
    Lindane is one of the 27 pesticides on the PIC list. PIC is an international procedure which requires exporters of certain particularly hazardous chemicals to inform the importing country of the chemical's legal status and its hazards. The process has recently changed from a voluntary code to an internationally binding convention. The purpose of PIC is to allow developing nations to make informed decisions about whether or not they wish to allow the import of hazardous chemicals.
    Lindane is a Persistent Organic Pollutant (POP) candidate. The POP Convention which will shortly start to be negotiated will seek to phase out the production and use of a range of chemicals which are classified as Persistent Organic Pollutants. Concern over these derives from the fact that many are used in tropical zones, but percolate through the globe environment to end up in cold regions such as Scandinavia, Canada and Antarctica. POP pesticides include many which have been banned in several countries and some whose production is believed to have ceased world-wide. Lindane is not currently in the list of POPs, but its inclusion has been proposed. This is likely to be resisted by industry and some governments who believe no alternatives exist to its use in some situations.
    In the third world, lindane is used for the control of a broad spectrum of plant-eating and soil-dwelling pests, public health pests and animal ectoparasites. Being an old chemical with no remaining patents it is relatively cheap, and its persistence is often seen as advantage in pest control rather than an environmental hazard.

Toxic effects
As with any other pesticide active ingredient, toxicity trials carried out in laboratories reveal a range of acute and chronic health effects. Acute exposure mainly effects the central nervous system with manifested symptoms including vomiting and diarrhoea followed by convulsions. Exposure to small amounts by skin contamination or ingestion have been known to lead to headaches, nausea, dizziness, tremors and muscular weakness. Lindane is classified by the World Health Organisation (WHO) as 'moderately hazardous' and has an oral LD50 in the rat of 88 mg/kg(1). This means that a dose of 88mg of lindane administered orally for each kg of body weight (bw) will kill 50% of a sample population of rats. Human volunteers ingesting a dose of 17 mg/kg have experienced severe toxic symptoms, and a lethal dose to an adult would be in the region of 0.7 - 1.4 g(2).
    Several cases of human poisoning by lindane have been reported. Children are significantly more susceptible to the toxic effects of lindane. In one case a dose equivalent to 62.5 mg/kg proved fatal, while the LD50 in the rat is above 88 mg/kg. In adults, doses above 300 mg/kg ingested orally have proved fatal(3).
    Since lindane has been in very widespread use for several decades, its long term health effects have been extensively studied. Included among the reported chronic effects of exposure to lindane are nervous disorders and increased liver weight.
    Trials to ascertain its carcinogenic potential have showed an increased incidence of benign and malignant liver tumours in mice when fed with doses of up to 600 mg/kg, but other animals did not produce such conclusive results(4). The international Agency for Research on Cancer (IARC) has concluded that lindane is a possible human carcinogen (class 2B), and the US EPA has classified it similarly as a class B2/C possible human carcinogen.

Exposure to lindane
As well as occupational exposure of workers who use lindane, and environmental exposure through residues which persist in the environment, new data demonstrates people may be exposed to lindane in surprisingly high quantities.
    The Acceptable Daily Intake (ADI) for lindane which has been determined by the international authority on food residues, Codex Alimentarius, is 0.001 milligrams per kilogram (mg/kg) of body weight. For a 60 kg adult therefore the maximum daily dose should not exceed 0.06 mg in total. The ADI was changed in 1997 from a previously less stringent figure of 0.008 mg/kg.
    Recent data published by Codex Alimentarius shows that a person consuming an average local diet in any region of the world will exceed the ADI for lindane by between 3.8 and 12 times. The highest consumption of lindane in food occurs in Europe where a theoretical maximum daily intake of lindane in a typical European diet would reach 0.742 mg, or 1237% of the ADI. The highest intake of lindane is likely to occur from consumption of cereals, red meat and tomatoes(5).

Key health issues
Aplastic anaemia
Exposure to lindane has been linked with blood disorders known as blood dyscrasias, and in particular the disorder aplastic anaemia where the formation of platelets and white cells is disrupted. A great deal of work has been produced both proposing and refuting a possible link between blood dyscrasias and exposure to lindane. However, an extensive review carried out by the UK Advisory Committee on Pesticides (ACP)(6)  has concluded that there is no conclusive link, but that in certain cases the development of the disease may be an idiosyncratic response to exposure to lindane. In many of the cases where patients who developed blood dyscrasias were exposed to lindane, they were also exposed to other pesticides. The ACP therefore concludes that lindane cannot be directly held responsible for causing the illness. The International Programme on Chemical Safety does not carry out an extensive review of the literature but reports that a number of cases of childhood aplastic anaemia were reputed to have been caused by lindane(7).

CHARGE
This condition which involves multiple congenital abnormalities has been linked to exposure of the mothers of CHARGE children to lindane during early pregnancy. A statistically significant proportion of mothers of CHARGE children in the UK were exposed to pesticides in early pregnancy, and one of the most prominent pesticides implicated was lindane(8).
    This issue was addressed by the Health and Safety Executive (HSE)(9) and in a parliamentary debate(10). HSE concluded that since mothers of CHARGE children were exposed to other chemicals in addition to lindane, no direct link can be proven. In the parliamentary debate where the issue was raised, no response was given by the Government.

Breast cancer
Lindane is an endocrine disruptor which is capable of imitating certain hormones in humans and thereby disrupting the physiological functions which these hormones control. There is a significant body of evidence which suggests that where lindane is used extensively, and particularly where cattle are exposed to it, the incidence of breast cancer is higher. The UK has one of the highest rates of death from breast cancer in the world, and in Lincolnshire where lindane is used extensively on sugar beet crops, the incidence rate of breast cancer is 40% higher than the national average(11).
    In 1995, the Green Network (Lincoln, UK) sent a breast cancer petition with 17,000 signatures to the European Parliament. It reflected the great public concern about breast cancer and the use of lindane in Lincolnshire.
    The UK Government has announced a breast screening programme with the aim of reducing the high rate of mortality from breast cancer. However, on current evidence there is no acceptance on the part of the Government that lindane is responsible for causing breast cancer(12).
    The presence of lindane in human milk has been reported in countries throughout the world(13). Lindane residues are similarly detectable in cows milk and it is therefore clear that children, who have already been described as being more susceptible to the toxic effects of lindane, are ingesting the chemical from birth, and probably from conception. Recent surveys of lindane in cows milk carried out by the UK-MAFF Working Party on Pesticide Residues (WPPR) have revealed detectable residue levels in 100% of 216 samples taken. Of these over 4% exceeded the Maximum Residue Limit (MRL)(14).

Environmental effects
Lindane is highly volatile, and when applied to field crops in particular, a high proportion (up to 90%) of the pesticide enters the atmosphere and is later deposited by rain. Concentrations of 5.5mg/l of lindane were detected in rain in Oxfordshire in 1992(15). Lindane is also leached into surface waters and even into ground water. For example, lindane contravened legally permissible limits in drinking water supplied by North West Water on two occasions in 1993(16). It has been found in increasing concentrations in the marine environment, and particularly in the North Sea(17).
    The International Conference on the Protection of the North Sea agreed to reduce emissions from land, rivers and the atmosphere of a number of toxic chemicals including lindane by 50% between 1985 and 1995. Implementation of this agreement in the UK is in the form of the 'red list' which includes lindane (gamma-HCH). The UK failed to meet its reduction targets, and that in fact emissions of lindane to the North Sea from the UK increased by up to 50% between 1990 and 1991(18). Figures published by the National Rivers Authority (NRA) (now part of the Environment Agency) show that total discharges of lindane from rivers to the North Sea increased between 1992 and 1993(19). Lindane has also been detected in the North Pacific, Persian Gulf, Arabian Sea, Red Sea, Western Pacific, Indian Ocean, Antarctic Ocean and Arctic Ocean(20).
    In common with other organochlorine pesticides lindane is fat soluble and this contributes to its tendency to bioaccumulate through food chains. Residues have been detected in the kidneys, livers and adipose tissue of a wide variety of wild animals and birds. It is highly toxic to aquatic invertebrates and fish

Regulatory status:
On 13 July 2000 the European Union Standing Committee on Plant Health voted for a ban on lindane with the support from UK and other Member States. The European Commission ratified the decision in December 2000, which should come into effect by the end of 2001. The ban will cover all agricultural and amateur gardening uses of lindane.  

The following countries have banned lindane for all uses(21):

The following countries have severely restricted the use of lindane:

Conclusions
Lindane has been in use long enough for a significant body of evidence on its toxic and environmental hazards to have built up. It has cause deaths and poisonings in humans and there is authoritative recognition of its long term health effects including carcinogenicity. It is a serious environmental contaminant and as well as being directly toxic to wildlife it bioaccumulates along food chains. A significant body of scientific and anecdotal evidence links lindane with serious health problems including aplastic anaemia, the birth disorder CHARGE and breast cancer.

References
1. International Programme on Chemical Safety, The WHO recommended classification of pesticides by hazard and guidelines to classification 1994-1995, UNEP/ILO/WHO 1994.
2. Brooks G T, Lindane: Faraday's hidden legacy, Pesticide Outlook 1,4, August 1990.
3. Health and Safety Executive Pesticides Registration Section, Evaluation on Gamma HCH (Lindane II), Ministry of Agriculture Fisheries and Food Pesticides Safety Division, December 1992.
4. IARC, IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans - Some halogenated hydrocarbons, IARC, October 1979.
5. Codex Alimentarius Commission, Consideration of intake of pesticide residues: Reports on pesticide residue intake studies at international and national level based on revised guidelines for predicting dietary intake of pesticide residues, Reports of 13TH session of the Codex committee on pesticide residues, FAO/WHO, April 1998.
6. Health and Safety Executive Pesticides Registration Section, op cit
7. International Programme on Chemical Safety, Environmental health criteria 124, Lindane, World Health Organization, Geneva, 1991.
8. Blake, Kim D and David Brown, CHARGE association looking at the future - the voice of a family support group, Child care health and development, 1993, 19, 395-409.
9. Health and Safety Executive, 1992, Op cit
10. Mackinlay, Andrew, MP, Parliamentary debate on Lindane, 31 March 1995
11. Women's Environmental Network, Lindane, WEN, 1994
12. Tom Sackville MP, Under-secretary of state for Health, in a debate on lindane in the House of Commons, 31 March 1995.
13. Moses, Marion, Pesticides and breast cancer, Pesticides News 22, December 1993, 3-5
14. Elevated lindane levels in milk, Pesticides News 32, June 1996, The Pesticides Trust [now PAN UK].
15. Harris GL, et al, Pesticide application and deposition - their importance to pesticide leaching to surface water, Proceedings of the Brighton Crop Protection Conference: Pests and diseases - 1992, Volume 2, 477-486, BCPC 1992.
16. Drinking water 1993: A report by the Chief Inspector, Drinking Water Inspectorate, HMSO, July 1994
17. Lohse, Joachim, Sabine Winterler and Dirk Susat, Lindane and other pesticides in the North Sea - A reason for concern, Greenpeace International, 1988.
18. Lyons, Gwynne, Meeting commitments? - A progress review of the UK's pledge to reduce North Sea inputs of red list substances by 50%, WWF 1994.
19. National Rivers Authority, Contaminants entering the sea, HMSO, May 1995.
20. International Programme on Chemical Safety, 1994. Op cit
21. UNEP, Import decisions as of 30 June 1988, Lindane (CAS:58-89-9).

[This article first appeared in Pesticides News No.28, December 1995, p28-29, updated July 2001]