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THE ADVERSE EFFECTS OF AGROCHEMICALS ON REPRODUCTIVE
HEALTH
(BOOKLET) Introduction The development of highly complex, chemical methods of pest control started around World War II, with the introduction of the first synthetic organochlorine (OC) insecticides, which included DDT, lindane (HCH), aldrin and dieldrin. The thousands of different pesticides manufactured today fall roughly into the following chemical categories; organochlorines, halogenated hydrocarbons, carbamates, heterocyclic compounds, organophosphates, chlorinated phenoxy substances, amines and ureas, benzonitriles, phenolic compounds and pyrethroids. They consist of a mixture of active ingredients; designed to destroy the pests, together with many other chemical additives, such as solvents, combined into usable products. The growth of the agrochemical industry since World War II has been enormous, and now covers the globe. It is estimated that the industry worldwide produces about 45-50,000 different pesticides based on about 600 active ingredients. In one year alone 23,504 tonnes of active ingredients were sold by UK pesticide manufacturers, which amounts to nearly 420g for a person in the UK population (2). The actual sales of pesticides by UK manufacturers increased from £30 million a year from the late 1940s to £150 million in the mid-1970s. In 1985, total sales of pesticides amounted to almost £900 million, of which approximately 60% was accounted for by export purposes (1-3). Pesticide manufacture is dominated by a few large chemical companies worldwide, including Ciba Geigy, Bayer and ICI. Many of these companies also have interests in other chemical productions, including the manufacture of pharmaceuticals (1,4).
Non-agricultural use of pesticides covers many areas. Local authorities use a great variety of pesticides in their parks, gardens, lawns, golf courses and similar recreation areas. British Rail contractors spray thousands of kilos of pesticides, largely atrazine and simazine, annually on to railways and their embankments. Herbicides and chemicals such as sodium chlorate, dichlorobenzil and diquat are applied around canals and various waterways to remove excessive weeds (1,2). Modern building practices primarily use lindane as an active ingredient in wood preservation treatments (7). The insecticide aldrin is used in the treatment of electric cables. Others are used at all stages of forest management (8). They are also used widely in domestic gardens. The most recent figures show that over the period 1982-1988, the sales in the garden herbicides increased by 20,9% and garden insecticides by 35,1% (3). Pesticides are also present in many other manufactured products, including wall paper pastes, marine and anti-fouling paints, wooden furniture, DIY products and natural-fibre textiles. New carpets are often treated with moth proofing chemicals, including common insecticides such as pyrethrums and lindane. Insecticides such as carbaryl, lindane and malathion are also found in pet delousing products as well as in some shampoos for controlling human head lice and scabies. In human medicine, warfarin, the rodenticide, which has an anticoagulant action, is frequently used in the prevention of blood clots (1). Traces of lindane, dieldrin, DDT and chlorpyrifos have also been found in some lanolin samples (9,10). They had not been added to lanolin for any specific purpose, but as lanolin is derived from sheep wool fat, the pesticide contamination was attributed to the use of sheep dips. As can be seen, the use of pesticides is extremely diverse. They are found in our foods, water, gardens, DIY cupboards, carpets, furniture, recreation grounds and even in our medicines and bathroom cabinets.
OCs are particularly harmful for all living systems, owing to their high affinity to fatty tissue, and to their persistence in the environment. Their half-lives have been found to be at least 20 years in both soil and water, with some soils retaining as much as 38% of the amount originally applied (1,2,11). Because of their solubility in fats, this group of pesticides can accumulate and transfer from one food chain to another, e.g. from insects to birds, to fish, and thence to larger mammals, including humans (12). This accumulative danger of OC pesticides led to their environmental ban in 1971 in the US. In the UK, they became subject to a voluntary ban from 1974 onwards. However, lindane (gamma HCH) is still widely used in the UK as an agricultural and horticultural insecticide, as a wood preservative, and as a treatment for head lice and scabies. Despite restrictions on their use, residues are still frequently found in many food products. After being banned, environmental levels of OC residues fell until the 1980s, since when they have remained fairly static. This has been attributed to the ever-increasing use of OC compounds for industrial purposes, as well as to their continued legal and possibly illegal use (1,2). A 1979-1980 analysis of 22 dietary samples found high levels of dieldrin in some milk and potato samples, as well as lindane in some meat, milk and poultry. While the average level in the group of samples were low, in some they still exceeded the current EC recommended Maximum Residue Level (MRL) (13). Other samples taken in 1985-1987 of strawberries, brussel sprouts and cabbages revealed that DDT levels exceeded the MRL recommendations (2). Other surveys have found dioxin and other OC residues in fruit, vegetable, meat and dairy products sampled (14-16). Persistent OC residues such as DDT, which is highly fat soluble, have been found in fat tissue of all humans tested. Government figures show that in 1977 the average DDT contamination in men was 2.6 ppm (parts per million) and in women 1.6 ppm, thus exceeding the current official EC MRL. In some men the DDT levels were found to exceed 15 times the EC legal limit, and in some women 17 times over the limit (17). Furthermore, traces of lindane and dieldrin were detected in 1979/80 UK survey in human milk samples (2). The presence of pesticide levels in human milk samples is apparently still quite common, particularly in developing countries. For example, high levels of aldrin have been recorded in human milk samples in India, while dieldrin levels have been found to be the highest in the breast milk in most South American countries (18). In addition, some infant foods have been found to be contaminated with pesticides. A 1987 Ministry of Agriculture, Fisheries and Food (MAFF) survey on 50 infant foods detected that 18 out of 31 samples of infant rusks contained pirimiphos methyl and three samples of cow's milk contained dieldrin at levels exceeding the EC MRL (12). These findings are alarming, as they show that exposure to pesticides can begin very early in human life, and particularly because DDT, dieldrin and aldrin have all been found to have carcinogenic, mutagenic and teratogenic action (2,19). Latest evidence also suggests that OC pesticides have mild oestrogenic properties and may thus able to precipitate labour. Studies in Brazil and in India have shown the levels of DDT to be significantly higher both in miscarried fetuses and in pre-term infants compared to infants born full-term (20,21). Recent research has suggested that an excessive exposure to OCs may be a cause for the presently appreciable decline in sperm density and quality, which is reflected in an overall reduction in male fertility (22,23). Even though lindane is considered to be slightly less toxic than other DDT-related products, it is still able to dissolve in water to form two toxic compounds, i.e. alpha- and beta- HCH (1). A recent study on marine environment has clearly demonstrated a relatively high level of lindane metabolites in marine environment (24). Lindane has been directly linked with both reproductive and carcinogenic properties (19). Organophosphates From the mid-1970s, when the persistent OCs were finally phased out of the agricultural market, they were replaced by highly toxic, but biodegradable, organophosphorus and carbarmate pesticides. Their toxic pedigree was established during World War II, when research was conducted to find potent nerve gases for military purposes. Virtually all types of organopesticides (OPs) target and depress acetylcholinesterase activity in a dose-dependent manner, leading to an excessive acetylcholine output, nerve paralysis and finally death. The acetylcholinesterase inhibition is non-specific, affecting the whole body systems via the cholinergic, muscarinic and nicotinic receptor pathways. The body systems affected are the central nervous system, the autonomic nervous system, as well as peripheral muscular pathways (2,25,26). Adverse Effects of Pesticides The London Food Commission conducted a thorough toxicological survey on active ingredients currently permitted for use by UK pesticide manufacturers. The results showed that out of 426 chemicals listed, 68 were found to be carcinogenic, 61 mutagenic and 35 were found to have various reproductive effects, ranging from impotency to a variety of birth defects. Furthermore, 93 were found to cause skin irritations and similar milder complications. In total, almost 40% of pesticides currently in use were linked with at least one adverse effect (19). Acute exposure: Chronic exposure:
Numerous studies have found a high incidence of cancers and related disorders in individuals occupationally exposed to pesticides (28-38). These include lung (39,40), kidney (41), and testicular cancers (42), leukaemias and multiple myelomas (43-49), mesenchymal and other tumours (50-52), non-Hodgkin's lymphomas and malignant lymphomas (53-58), soft-tissue sarcomas (59-61) and brain gliomas (62,63). The most common pesticides which have been found to be carcinogenic include, aldrin, benomyl, captafol, captan, lindane, 2,4-D, maneb, mancozeb, thiram and zineb (2,19). It has also been suggested that a chronic low-level exposure to any carcinogenic substances, including pesticides, from early infancy may lead to cancer formation later in life. The pesticides listed in this study were; captan, chlorothaoil, folpet, ethylene thiourea, acephate, parathion and methyl parathion (64). Reproductive Effects The London Food Commission has listed 35 different pesticides that have been linked with adverse reproductive effects in animal studies. The findings include such widely used formulations as; aldrin, benomyl, captan, carbaryl, dieldrin, dinoseb, ioxynil, lindane, maneb and paraquat (19). Mutagenicity: Teratogenity:
The anticholinesterase activity of organophosphates (OPs) results in an excess of acetylcholine activity, primarily in the muscarinic receptors (96). Chronic exposure to OPs has been found to result in a gradual loss of brain stem cholinergic muscarinic and nicotinic (97-101) and serotonergic (102,103) receptors, as well as to an increased permeability of blood-brain barrier (104). It has been now established, through animal experiments, that perinatal exposure to OPs can cause negativre neurobehavioural effects in the offspring. For example, rats exposed to OPs gavre birth to pups with an impairment in endurance and coordination, as well as a reduction in the number of brain neurotransmitter receptor sites. It was concluded that OPs can act as neurobehavioural teratogens, causing behavioural abnormalities in the offspring without any other outwardly noticeable effects (105,106). Chronic post-natal exposure to OPs has also been linked with other psychiatric manifestations, such as long-term changes in brain function when measured by the electroencephalogram (107), aggression (108), memory difficulties, depression, emotional instability and schizophrenic reactions (109-111). Delayed Neurotoxicity Several cases of organophosphate induced delayed polyneurophathy have been reported in the literature (112- 120), in some instances affecting thousands of individuals (121). In addition, sclerosis of myelinated axons, in which demyelination is a secondary response to axonal degeneration, has consistently been associated with OP-induced delayed neurotoxicity (25,122,123). Consequently, several aetiological correlations have been made between those occupationally exposed to OPs and the development of multiple sclerosis (25,124-126), Motor neurone and Parkinson's disease (25,127,128), muscular dystrophy (25,130,131), Wernicke's encephalopathy (25,129) and Guillan Barre-like syndromes (25,130). Allergies and Other Immuno-Regulatory Disorders In humans, chronic OP exposure is able to disrupt serotogenically mediated immunoregulation (25), leading to a a prolonged suppression of T-lymphocytes and an elevation of B-lymphocytes (25,131-133). Interleukin 2 and natural killer cell activity also seem to be affected (25,134,135). Consequently, chronic OP exposure has been linked with the development of allergies and other immunoregulatory disorders, such as chronic fatigue syndrome and myalgic encephalomyelitis. (25,136-138). Pesticides in the Environment Food: Water: Besides pesticides and other industrial pollutants, nitrates are also widely detected in UK drinking water supplies. This is due to ever-increasing amounts of nitrogenbased fertilizers being added to the soil. In the late 1930s 60,000 tonnes of nitrogen fertilizers were spread on agricultural land in UK each year, increasing to 1,580,000 tonnes by 1985 (144). Only about half of the fertilizers applied is taken up by the crop, the other half being lost in a variety of ways, e.g. by denitrification into the atmospnere, by combining into the soil's organic matter and by leaching into surface or ground water reservoirs (145,146). As the result of nitrates leaching to the water supply, it is estimated that at present approximately 1,000,000 people in UK are exposed to nitrate levels in drinking water exceeding the present MAC level and, if no action is taken, this figure will rise by the early part of the next century to an estimated of 4,600,000 individuals (147). High nitrite, derived from high nitrate, has been linked with the 'blue baby' syndrome due to methaemoglobinaemia. The N-nitroso group are considered to be among the most powerful chemical carcinogens and have been found to cause cancer in 39 animal species studied, including primates (19,148-151). Nitrogen is a vital element found in all plant, soil, air, water and arumal pathways. The crucial questions is, however, whether indiscriminate use of inorganic nitrogen in agriculture is either necessary or appropriate, as it has already caused a widespread eutrophication in most UK waterways, leading to the suffocation and death of several river, lake and marine species (19). The use of nitrogen fertilizers also affects the nutritional value of crops, as farmers are able to grow, with the help of the fertilizers, an abundance of green foliage, practically devoid of essential trace elements (152,153). Recent crop and soil investigations found particularly low levels of manganese, zinc and iron in the samples studied (154-156). Manganese deficiency has been linked with a wide range of metabolic defects, including congenital malformations (157). Zinc deficiency in turn can lead to premature delivery, small for gestational age babies and/or congenital malformations (158). Testing the Toxicity of Pesticides Most current research into the toxicity of pesticides uses tests of a single compound LD (lethal dose) on animals (143). However, unlike these test conditions the general human population is exposed intermittently to a great combination of pesticide residues daily for many years at very low doses. The outcome of this type of longterm, chronic exposure is quite impossible to determine using animal experiments (159). Furthermore, animal tests, when clearly positive, could be a complete waste of time, as humans do not necessarily respond to substances in the same way as animals do, and vice versa. For example, 2-napthylamine has been found to be a bladder carcinogen in humans and dogs, but not in mice, rats, guinea pigs and rabbits (160). Morphine excites cats, but is used as an anaesthetic in humans. Arsenic kills humans, but is harmless to guinea pigs, chickens and monkeys. Digitalis raises blood pressure in dogs, but lowers it in humans (161). The other factor which must be taken into account is the synergistic effect of pesticides, which may lead to increased toxicity. For example, studies have found that when the fungicide perchloraz was given to birds along with the insecticide malathion, there was a dramatic increase in bird deaths over that expected from the same dose of each pesticide given alone. Similar interactions have been also found to occur between dimethoate and chlorpyrifos with perchloraz (162). This phenomenon was indeed noticed by the the Government Steering Group on Food Surveillance, as they state: "At present toxicological interpretation is particularly difficult where residues of more than one pesticide is found in the same food sample" (12). A similar point has been expressed by WHO about the mixture of pesticides currently found in the drinking water samples. They observed that "the problem of exposure to any mixture of two or more herbicides cannot be handled in isolation. Drinking water may contain chemical residues of different types, including pesticides and other contaminants. In addition, people are exposed to chemical substances by many other routes, which may give rise to possible interactions" (163). Problems of Resistance and Persistence In 1986 Goldsmith and Hildyard produced a report which commented critically on the level of current pesticide production and use in the UK agricultural market. They write: "In three years, between 1974 and 1977, the area of cereals sprayed with aphicides increased 19 times. Between 1979 and 1982, the area of crops treated with insecticides has doubled, while the area treated with fungicides more than doubled. BAA figures from 1979 and 1982 for the major crops grown in Britain (cereals, potatoes, oilseed rape, sugar beet and peas) has shown a 29% increase in the area sprayed with herbicides, a 39% increase for insecticides and a 106% increase in fungicides. Yet the actual cropped area only increased four per cent " (164). One explanation for this discrepancy could be the increasing number of pesticide-resistant pests (165). The first reports of herbicide resistance appeared as long as 1969, since when numerous reports have appeared (166,167). Currently, 50 different herbicide-resistant weed species (166,168) have been identified, while the number of insecticide-resistant insects is also growing at an alarming rate (169). As a consequence, the agrochemical industry is busily developing new chemicals, designed to destroy a narrower and narrower range of target species. A resulting problem, however, is that many of these agrochemicals do not decay in the soil, as it had been first predicted. For example, the 1987 British Geological Survey (BSG) on the Pollution of Agriculture Pesticides and Solvents found that the assumption that agrochemicals decay quickly in the soil, or simply evaporate, is no longer valid. Although some compounds are rapidly hydrolysed in water, others break down very slowly and thus can percolate swiftly into aquifiers, particularly through sandy or chalky soils (170). When these chemicals penetrate ground-water supplies, pollution can affect the same supply for years to come (171). Among the most widely spread and most problematic pesticides are some herbicides, especially the carboxyacid and phenylurea groups, as well as chlorinated solvents (170).
Excessive food production among the EC countries is a very real problem. Millions of pounds of fruit and vegetables are destroyed, distilled to alcohol or fed to animals each month. For example, during a period of 4 months, 605,518 tonnes of apples, 285,702 tonnes of peaches and 164,357 tonnes of oranges were destroyed at the staggering cost of £67,000,000 (172). The tax-payer is effectively paying three times for this fiasco: by subsidising surplus and unwanted agricultural production, by paying to clean up resultant pollution, and by paying for the medication needed to treat health problems associated with agrochemicals. The irony here is that the companies which manufacture the toxic agrochemicals are very often those who also manufacture the medication. The following recommendations are made with a view to improve the current situation:
Conclusion Current agricultural policy benefits only a small number of corporate farmers and the agrochemical companies. Far more consideration should now be given to the small, independent farmer and to the consumer. Few areas of government policy is so intimately concerned with individual consumers as are the provision of safe nutritious food to eat and clean water to drink. In order to start to reduce present high-level agrochemical use and contamination, government policy should be to motivate farmers to adopt effective integrated pest management strategies, which combine traditional farming methods, such as crop rotation, fallowing, manual feeding, etc., with artificial pest controls. Furthermore, full financial support should be available to any farmer wishing to adapt to organic farming practices. ACKNOWLEDGEMENTS: This study was supported by as grant from FORESIGHT, The Association for the Promotion of Preconceptual Care. A special recognition is given to Mrs Belinda Barnes who has fought tirelessly to draw attention to the harmful effects of agrochemicals on reproduction and health.
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