Pesticides are used in farming and horticulture to control weeds, fungi, insects and other pests and to influence the growth of crops such as fruit, vegetables and cereals. In Denmark, there are at present about 90 authorised active ingredients, which are used in approx. 550 products.

Over the years, the requirements for authorisation of the individual pesticides have been considerably tightened. As a result, some pesticides have been banned on account of their undesirable environmental and/or health properties. This applies, for example, to a number of pesticides containing chlorine, such as DDT, dieldrin, etc. However, owing to their lack of degradability, they are still found in the environment, from which they find their way into food products.

Pesticides are widely used. Within the food sector, it is particularly in connection with the production of fruit and vegetables that the risk of a residual content is greatest.

Extensive use is also made of pesticides, in the form of herbicides and fungicides, in the cultivation of cereals and to regulate growth. The crop is often sprayed long before it is harvested, so the degradation of the pesticide can be advanced. When a crop is sprayed a shorter time before harvest, it must normally be expected to have a residual content of the pesticide.

Acute and chronic effects of pesticides have been investigated in numerous experimental studies and in studies of persons with occupational exposure, both in Denmark and in other countries. Apart from high-dose exposure in connection with accidents or suicide, the general public in Denmark is subject mainly to low-dose exposure, primarily as a consequence of pesticide residues in food and drinking water or from private use of pesticides in or around the home.

Population studies

There are only extremely sparse epidemiological data concerning health effects among the general population as a consequence of low-dose exposure to pesticides. There are differences in both exposure and sensitivity to pesticides in the population, depending on age, sex, eating habits, environmental factors and/or lifestyle. Some sections of the population must thus be expected to show health effects from exposure to significantly lower doses of pesticides than those causing effects in the rest of the population. Children are a special risk group, particularly due to qualitative and quantitative differences between children and adults in their intake of different types of food. Other risk groups may be persons with a poor immune system or persons with certain chronic diseases. For further amplification of the effect of pesticides on public health, readers are referred to Skadhauge (1998).

Metabolites

In living organisms, pesticides are transformed into metabolites. The documentation on which the authorisation of pesticides is based normally includes information on most of the metabolites from the substance in question, but separate toxicological investigations of the individual metabolites are not normally performed. The toxic effect of metabolites is generally thought to be lower than that of the original substance because the metabolites are often more water-soluble and are thus eliminated faster from the organism (Hayes, Laws 1991). However, there are some important exceptions, where biotransformation results in a more toxic product (e.g. the formation of oxon derivatives of organothiophosphorous pesticides or the formation of epoxy compounds from certain insecticides, such as dieldrin and heptachlor). Atrazine’s metabolites, deethylatrazine and desisopropylatrazine, are more acutely toxic than atrazine; they leach more easily than the original pesticide and may thus be a bigger problem. Where there is knowledge about such metabolites, it is taken into account in the authorisation procedure and in connection with the setting of limit values in food.

6.2.2 Risk population and individual vulnerability

In the case of exposure to a potential toxic factor, the risk population is traditionally taken to be the part of the population that is subject to 1) increased exposure, 2) increased dose with the same exposure, 3) increased effect with the same exposure in relation to the rest of the population.

Increased exposure can occur in the case of accidents or occupational exposure, but it can, for example, also occur to some extent in population groups with special eating habits (e.g. vegetarians or persons with another food base) or neighbouring on sprayed land.

Children as a risk group

Children are a risk group because they are often exposed to a larger dose of pesticides than adults with the same type of exposure. Owing to more rapid breathing in relation to their body weight than adults, children inhale relatively more air. Children’s special diet patterns and intake of pesticide residues are the subject of a report from the American National Research Council (NRC). Here, both qualitative and quantitative differences were found between children and adults with respect to exposure (National Research Council 1993). Firstly, children take in more energy per kg body weight than adults and, secondly, children eat far fewer types of food than adults. In addition, the intake of water, both in the form of drinking water and as a food component, differs greatly between children and adults. The council concluded that differences in diet and thus in dietary exposure to pesticide residues could explain most of the differences in pesticide-related health risks between children and adults. Differences in exposure were generally a more important cause of differences in risk than age-related differences in the way the substances act in the organism. However, the council found that, among other things, effects on neurological and immunological development processes were insufficiently clarified.

With respect to an increased effect with the same exposure to pesticides, there is agreement that foetuses and children are a special risk group (Goldman 1995; Reigart 1995). As stated in the above-mentioned report from NRC, there are both qualitative and quantitative differences between children and adults with respect to the toxicity of chemical substances, including pesticides (National Research Council 1993). The report gives examples, mostly concerning medical drugs, where children are more or less sensitive to the individual substances. These differences result from the fact that the substances are degraded at a different rate in the body in children than in adults and from the greater or lesser toxicity of the degradation products compared with the parent substance. The qualitative differences in toxicity are due to exposure in particularly sensitive periods in early development, when exposure to a toxic substance can permanently change the structure or function of an organ system. The quantitative differences in toxicity between children and adults are due partly to age-related differences in absorption, metabolism, detoxification and excretion of the environmentally foreign substances and partly to differences in size, not fully developed biochemical and physiological functions and variations in the composition of the body (water, fat, protein and mineral content), all of which can affect the degree of toxicity. Since new-born infants are the group that differ most from adults, anatomically and physiologically, they must be regarded as having the most pronounced quantitative differences in sensitivity to pesticides. The report found that quantitative differences in toxicity between children and adults were normally lower than a factor of 10.

With reference to the foregoing, the US Environmental Protection Agency (US-EPA) estimates that children constitute a special risk group. Accordingly, in individual cases in the USA, an extra uncertainty factor of 100 is used when setting maximum limit values in connection with risk analyses that are based on animal tests and that are not deemed to throw sufficient light on the special situation of children. Examples of such substances and the related uncertainty factors (in brackets with the year) are: heptachlor (200 in 1990), triazophos (500 in 1990), fentin (200 in 1970; 500 in 1991), abamectin (500 in 1992), amitrol (provisional uncertainty factor of 1000 in 1993), phosalon (200 in 1993) and propylene thiourea (metabolite of probineb, 1000 in 1993).

Other risk groups

Pregnant women, the elderly and persons with a poorly functioning immune system are other groups that must be presumed to be particularly at risk with respect to health effects from exposure to pesticides.

6.2.3 Exposure of the population

The general population can be exposed to pesticides through their intake of pesticide residues in food and via drinking water or through use of pesticides in and around the home, schools, offices, public parks and farms (drift and evaporation). Exposure can also occur through accidents, leakages due to incorrect storage, spills and pollution from production plants or landfill sites. Children, in particular, can be exposed to pesticides from eating contaminated soil, from contact with pets treated with pesticides or from parents exposed to pesticides in their work.

Exposure in the home

Exposure to pesticides can occur in connection with their use in and around the home, e.g. in combating insects and treating pets. Besides direct indoor treatment with pesticides, pesticides can be given off by pot plants treated with pesticides at the nursery. There have been no studies of this exposure in Denmark (Skadhauge 1998).

Exposure via food

The main exposure of the population to pesticides must be assumed to occur via food. Around 60% of this intake occurs via imported food products. Exposure via vegetables and, particularly, via berries and fruit predominates. The sources of the information on this are the Veterinary and Food Administrations’ annual reports on the nationwide control and monitoring of the residual content of pesticides in vegetable and animal food products on the Danish market. The samples are extracted at the wholesale level. The studies cover both Danish and imported food products and are carried out as a random sample control, supplemented by targeted control.

Figure 6.3
Frequency of fruit and vegetables with pesticide residues for Danish and imported crops, 1993-1997 (fruit and vegetables with the highest number of samples are presented). On average, pesticide residues have been detected in about one quarter of the Danish and imported fruit shown in the figure. For the vegetables, pesticide residues have been detected in an average of 20% of the imported vegetables in the figure, compared with 6% of the Danish vegetables.

Figure text:
frugt = fruit
æbler = apples
solbær = blackcurrants
ribs = redcurrants
pære = pears
kirsebær = cherries
jordbær = strawberries
hindbær = raspberries
blomme = plums

grøntsager = vegetables
tomat = tomatoes
salat = lettuce
kinakål = Chinese cabbage
kartofler = potatoes
gulerod = carrots
courget = courgette
bladselleri = celery
agurk = cucumber
importeret = imported
dansk = Danish

Food products

In the national monitoring programme, the samples are extracted at random (randomised) from the crops that it has been decided to check in the year in question. The programme is designed to determine the level of residues in the crops checked. The samples are taken at wholesalers, producers and importers. The sampling is carried out by the food inspection units, together with the Plant Directorate and the Danish Veterinary and Food Administration. The samples are generally extracted with a geographical distribution and distributed over the whole of the year In the case of fruit and vegetables, samples are taken weekly. In 1997 1,947 samples were extracted – 83% fruit and vegetables (1,613 samples), 3% honey (Danish and imported), 8% meat, 6% cereal (including 1/3 imported cereal). The 1,613 samples of fruit and vegetables comprised 919 samples of imported products and 694 Danish products. In both 1996 and 1997, the monitoring programme constituted about 0.0002% of the Danish production of vegetables, fruit and berries.

The national monitoring programme

In the last couple of years, studies of fruit and vegetables have covered about 150 different pesticides, comprising commonly used insecticides and fungicides and some herbicides. When the substance profile for the programme is set, the substances that have Danish MRL-values (MRL = Maximum Residue Limit; often corresponding to EU MRL-values) and/or are used here in Denmark are prioritised. Otherwise, the pesticides with low MRL-values or that are widely used are prioritised. Animal products and fish are checked for organochlorine pesticides, which used to be authorised for use and now occur as widespread environmental pollution. At the same time, the samples are tested for the industrial chemical PCB. In addition, a number of pesticides containing chlorine occur in fish – particularly oily fish. Since these substances have long since been banned, they are regulated and treated as environmental pollution. The occurrence of these substances in fish would not be affected by a reduction or possible phasing out of pesticides in Denmark.

Special investigations (targeted control)

In addition, special investigations are carried out, including so-called targeted control, that is used where and when it is suspected that current MRL-values are being exceeded. The suspicion can, for example, arise in connection with the current monitoring programme. The nature and scope of the targeted control vary from case to case and comprise two or more samples extracted at the retail and/or wholesale level.

Exceedances of limit values

For many years, the analyses carried out have shown that pesticide residues in food products on the Danish market generally meet the current regulations. The content has been found to exceed the MRL-values in 1-2% of the samples, but rarely by more than 50-100%. It is characteristic of the analyses that, with the reporting limits used, no residues were found in most of the samples. Normally, residues are detected in one third or less of the samples tested. As shown in figure 6.3, the detection frequency is higher in samples of imported food products than in Danish food products, but within the individual crops, the detections vary, both qualitatively and quantitatively from year to year, depending on economic and climatic conditions and on differences in the need for treatment (Büchert 1998). In 1996, the most frequently detected pesticides were (in alphabetical order): captan, carbendazim, chlorothalonil, dithiocarbamates, endosulfan (sum), iprodione, quintozene, tolylfluanide and vinclozolin. None of the finds gave the Veterinary & Food Administration cause for concern with respect to public health (Büchert, Engell 1998).

Finds and exceedances in relation to crops

The monitoring programme indicates a tendency towards relatively more detections of residues in fruit, including citrus fruit and grapes, than in vegetables such as cabbage and potatoes. The total human average intake of pesticides is dominated by citrus fruit in particular (oranges and mandarins), potatoes and apples and, to a slightly lesser extent, tomatoes, pears, grapes and strawberries, which account for most of the load. However, the sum of these substances covers pesticide residues with very different toxicological properties, so the substances are not directly comparable and their combined action is not known. The Ministry of Food, Agriculture and Fisheries has initiated a study that will throw light on these questions within some years. Another important factor in connection with the summation of the pesticide residues in food products is that it does not include reduction factors. Some of the pesticide residues are removed during preparation - for example, peeling of oranges, mandarins, etc., the peel of which is seldom used. However, there are as yet insufficient data to clarify the size of the reduction factors in Danish diet. This aspect will also be looked at in a new study initiated by the Ministry of Food, Agriculture and Fisheries. A closer comparison of the individual food products and their significance for the intake of pesticides, and thus their possible toxic effects, is difficult for several reasons, including the fact that the data are often too limited, but also because the individual pesticides have different toxicological properties. It must be mentioned, however, that the higher detection rate in imported crops reflects the fact that, for comparable crops, there tend to be fewer positive results in Danish products than in imported ones. This tendency is most pronounced for crops like tomatoes, cucumber and peppers, which are greenhouse crops in Denmark but outdoor crops in other countries. However, the tendency does not apply to all crops. There are also examples, e.g. blackcurrants, where pesticide residues are more frequent in Danish crops than in imported ones.

Calculation of pesticide intake from food products and drinking water on the Danish market

The following calculation of the Danes’ intake of pesticides through their diet is based on monitoring data from the Danish Veterinary & Food Administration’s national monitoring programme in 1996 and 1997 (Büchert 1998). These data are not only the latest data but were also obtained with comparable methods and reporting limits. It is characteristic that no content was detected in most of the samples tested. Regardless of this, it must be assumed that treated crops always have a certain residual content, so that lack of detection can only be taken to mean that the content, if any, is below the analytical detection limit.

Methods of calculation

Different models can be used to calculate the pesticide intake from crops in which no residual content has been detected. In situations in which there are sufficient data above the detection limit, the distribution under the detection limit can be determined with reasonable statistical certainty. Unfortunately, that is not the case with the available monitoring data. The residual content in samples without a detected content must therefore be expressed in a different way – for example, by putting the pesticide content at 0 (zero) or, conversely, by assuming that it corresponds to the detection limit. However, both are rather rough approximations.

In this connection it must be stressed that the analytical detection limit is not a fixed quantity. It varies from one pesticide to another and from crop to crop, just as there is a variation from one analysis to another of the same substance in the same crop. However, since the exact data are not directly accessible, the calculations are based on the more general detection limits, which are determined for the individual substances during the validation of the methods. The residual concentration in samples with concentrations above the detection limit are estimated as the mean value between the highest and lowest detected content.

The scope of the calculations

The calculations of the content in the crops analysed have been carried out for all the pesticides detected in the analyses in 1996 and 1997. It was anticipated that there was a content in both Danish and foreign crops of the same type, also when the substance was only detected in crops of one or the other origin. There is also an overestimation, in that the calculations are based on an assumption that detection of a pesticide in a single type of crop means that the entire production of the crop in question has been treated with the pesticide in question and therefore has a residual content of the pesticide that differs from 0.

The calculations do not take into account intake of pesticides that have not been detected in the national monitoring programme in either Danish or imported crops, nor do they include any intake of such substances as might occur in contents below the analytical detection limits or that are not covered by the analytical methods used.

In the calculation of Danish consumers’ exposure to pesticide residues through food, the crops’ estimated content is multiplied by the average daily dietary consumption of the crop in question. The dietary data used are based on diet studies from 1985 and 1995 and on trade statistics.

Variations in the population

In practice, of course, there are many deviations in the population from the average diet model with respect to sex, age, ethnic background and social conditions. For a more detailed risk analysis for such groups there is thus a need for more precise dietary data. However, it must be stressed that the model set up provides a reasonable possibility of a more general evaluation of the pesticide intake on a national level, including the broader significance of keeping Danish crops free of pesticide treatment.

The distribution between Danish and imported food products

Good data on the distribution of Danish consumption between Danish and imported crops are not available. The main reason for that is, that with the "internal market", official statistics are no longer kept of imports and exports between the Member States. In the calculations carried out, the distribution has been estimated on the basis of earlier trade figures and agricultural statistics. These indicate that the distribution between imports and domestic production is 1:1 for such fruit as apples, pears, plums, berries, etc., while exotic fruit, such as citrus fruit and kiwi are exclusively imported crops. For vegetables, the distribution is about 1:4, although not for cucumber, tomatoes and similar, where imports, distributed over the whole year, account for about 70% of the total consumption. In the case of cereals, maize and rice are exclusively imported crops, while the consumption of barley is based entirely on Danish products. In the case of rye, wheat and oats, 5%, 20% and 65%, respectively, of consumption is covered by imports.

Table 6.2 shows the average daily consumption of Danish and imported cereal and cereal products in Denmark.

Table 6.2
Average consumption of Danish and imported cereal and cereal products, given in grammes per day.

The Danes’ dietary pattern

The variation in the Danish consumers' dietary pattern can be judged on the basis of the National Food Agency's dietary study in 1995. The results of that study, which covered more than 1,800 persons, are summarised in table 6.3 below, which gives the average intake and selected fractiles for the adult part of the population.

Table 6.3
Variation in Danish diet, given in g/day for adults m/f (Büchert 1998).

On the basis of the values in table 6.3 it can be calculated that the 90% fractile for dietary consumption of vegetables is about 225% of the mean intake, while, for fruit, it is about 300% and for cereal products, about 200%. The uncertainty on the figures is reflected by the fact that the values for the 90% fractiles are of the same order of magnitude as the sum of the mean content and the standard deviation. It must be added that the probabilities have not been calculated for how population groups and individuals compose their dietary consumption.

6.2.4 Calculations of the population’s intake of pesticides

Reduction factors and adjustments

The intake calculations for fruit and vegetables, which, as described, are based on monitoring data, reflect the occurrence of pesticides in the raw produce, so account is not taken of the reduction of the content during preparation of the raw produce (peeling, boiling, etc.). This is because the literature contains only limited information about such reduction factors and the data are usually of such a nature that they cannot be applied to Danish conditions. Therefore, reduction factors have not been included in the current calculations of the intake of fruit and vegetables, which leads to overestimation of the intakes in relation to the real values. A lack of data on the proportion of a given crop that has been treated with a specific pesticide has also made it impossible to adjust for actual use. This applies particularly to imported products and means that, for example, the intake from citrus fruit – and thus from imported crops – has been overestimated.

Estimated intake from fruit and vegetables

The intake of pesticide residues through diet has been calculated for all the pesticides detected in the analyses of fruit and vegetables in 1996 and 1997. The intake from Danish crops and from imported crops has been calculated separately, without detailed specification of the origin of the crops (for details, see Büchert 1998). The results show a total average intake of pesticides from fruit and vegetables of about 165 microgrammes per day. The intake of six pesticides/pesticide groups – carbendazim, dithiocarbamats, iprodione, o-phenyl-phenol, procymidone and thiabendazole – corresponds to half the total intake, while the other half is distributed over about 60 individual compounds.

The calculated total intake of pesticides from fruit and vegetables is made up of around 165 microgrammes per day is approx. 60 microgrammes per day, corresponding to 36%, from Danish crops and approx. 105 microgrammes/day, corresponding to 64%, from imported crops.

It must be stressed that any size comparison of the calculated intakes should be seen in the light of the fact that the pesticides have different toxic properties and potency. A small intake of a potent substance may thus very well be more dangerous from a health point of view than a large intake of a less potent substance.

Comparison with ADI

For the pesticides that are authorised for use on edible crops, an acceptable daily intake (ADI) is fixed on the basis of the same principles as for additives, and with a requirement concerning similarly comprehensive data. ADI for pesticides is set to protect against possible long-term effects. ADI is fixed on the basis of animal tests. In each test, NOAEL (No Observed Adverse Effect Level) is fixed as the dosage that does not have any harmful effect. ADI is fixed by taking the NOAEL from the most sensitive test on animals and reducing this by an uncertainty factor that must take account of the uncertainty that lies in extrapolating from animals to humans and the variations in people’s sensitivity and lifestyle. By international agreement, an uncertainty factor of 100 is used as the basis.

A comparison has been carried out between the calculated intakes and the upper limits recommended by the experts for acceptable intakes for a person weighing 70 kg, calculated as the ADI values multiplied by the weight (ADI mg/kg bw/day times 70 kg). All the calculated intakes constitute only a small part of the intake that could be accepted without giving rise to health concerns. The mean value of the calculated intakes of the individual pesticides is 0.31% of the upper limit for their acceptable daily intakes, with a standard variation of 0.46% and with the highest individual value (for methidathion) of about 2.2%. Even with big variations in the dietary consumption of the individual crops, the consumers would remain below the ADI values.

The variations in the exposure to pesticides via fruit and vegetables have been clarified by calculating the intake at the 90% fractile. The 90% fractile for vegetables and fruit has been put at 225% and 300%, respectively, on the mean value for the group of crops in question.

An evaluation of the maximum exposures of the population can best be based on the calculated mean intakes and the values given in table 6.3 for the entire group of vegetables or fruit. An evaluation of the intake via the individual crops can also be based on the data, whereas a summation of the maximum contribution from the individual crops is not possible without calculating the probability of the same person or population group having maximum consumption of several combinations of types of crop and determining the types of crop in question. On the face of it, it is believed that a conjuncture of maximum consumption of two or more crops would be exceptional and that a major consumer of a crop would normally have a limited consumption of other types of crop. In other words, if there were a maximum exposure to pesticides via one type of crop, the exposure to the others would often be correspondingly smaller.

Estimated intake from cereals and cereal products

Since 1987, cereals and bran have been included in the regular analyses of pesticide residues in food products on the Danish market. The analyses have been carried out with a changing search profile from year to year. In the last couple of years, the samples have been analysed with a multi-method covering 24 different substances. In 1997, a special analysis was carried out of the residual content of the straw-shortening products chlormequate and mepiquate. The analyses showed that the residual content of pesticides in cereals and cereal products meets current limit values, although, generally speaking, the data are too slender for a more refined analysis of the population’s exposure to pesticides from products of this type. The highest content of chlormequate – 3.8 mg per kg – was found in a sample of rolled oats from the UK. There are generally more and higher finds in Danish cereal products than in the imported products, and pesticides have been detected in almost all samples except in rice and in a sample of organic wheat. For a detailed review, readers are referred to Granby and Poulsen (1998). The calculations of the intake were based on a more conservative estimate of the residual content in the types of crop in question. The calculations were carried out in the same way as for fruit and vegetables, but covered all the pesticides detected in the entire period from 1987 to 1997.

Reduction factor

In the calculations, no direct differentiation was made between whether the residual content was detected in bran, in grain or in flour. If a substance was detected in one type of product, it was assumed that the substance was also present in others. It will normally be bran that has the largest residual content, and the residual content in flour will normally be reduced when the husks are removed and be reduced still further when the grain is milled and when the flour is baked into bread (bread was not included in the analysis). On the other hand, most of the pesticide residues will normally be in the bran product. In the case of chlormequate, it was found that milling of wheat grain into flour reduced the residues by a factor of about 4. For this reason, in the calculation of the intake from cereals and cereal products, it was assumed, as a cautious estimate, that the residual contents were reduced by a factor of 2 in relation to the measured content. In 1997, 21 bran samples were extracted (18 wheat bran and 3 oat bran), which were analysed for 26 pesticides. None of the samples exceeded the limit values, even though the residual contents were higher in bran than in whole grains and flour. However, reservation must be made for the fact that the analyses for glyphosate were of limited scope.

The results of the calculations are summarised in table 6.4, which shows the calculated pesticide intake with and without reduction through processing of the cereal. As will be seen from the table, the average intake is estimated to be about 26 microgrammes per day, with a distribution of about 2/3 from cereals produced in Denmark and 1/3 from imported cereals.

Bromide from fumigation with methyl bromide

It should be noted that the residual content of bromide is not included in the summation of the total intake. Bromide is not in itself a pesticide but is included in the analyses as an expression of any use of methyl bromide, which is used to fumigate cereals and other products. The test method for measuring methyl bromide is based on determination of bromide, but as this also exists in nature, it is a question of measuring whether the bromide content is higher than the normal content in the cereal product. In other words, the absolute content of bromide does not correspond to the residual content of methyl bromide, and it would be a gross over-estimation to include the bromide content when summing the total intake.

As in the case of fruit and vegetables, the average intake of the individual pesticide residues from cereals and cereal products is typically less than 1% of the ADI values (see Büchert 1998).

The variations in the exposure to pesticides from cereals and cereal products can be estimated from table 6.3, from which it will be seen that the 90% fractile for cereals and cereal products corresponds to approx. 200% of the mean intake.

Table 6.4 Look here!
Estimated pesticide intake from imported and Danish cereals and cereal products (Büchert 1998). There are very few analyses of glyphosate in cereals and cereal products. Empty spaces indicate that residues have not been detected. The analyses included pesticides that were not detected in any of the samples.

The estimated intake from animal food products and fish

The Danish Veterinary & Food Administration has been monitoring the content of pesticide residues in animal food products for many years. The analyses have primarily been directed at the chlorinated pesticides, such as DDT, HCB and similar fat-soluble compounds, but analyses have also been carried out for residues of organophosphorous pesticides in meat.

No residual content of organophosphorous pesticides has been detected in meat, but a chronic content of chlorinated pesticide residues has been found in both animal food products and fish. However, this residual content represents substances that have been banned in pesticides for many years. Their occurrence in the food products is therefore a result of their earlier use, which has resulted in extensive and permanent environmental pollution with these persistent substances.

Since the exposure of the consumers to pesticide residues from animal food products and fish is primarily a question of "the sins of the past" and does not concern the pesticides authorised for use today, the exposure does not depend on the extent of the use of the pesticides currently used in Denmark.

The estimated intake from drinking water

In the last few years it has been recognised that there is widespread pollution of our groundwater with pesticides. There is therefore a potential risk of such contaminants in our drinking water and thus a risk of exposure of the population through the water.

Since drinking-water wells in which a residual content has been detected have hitherto been closed, the real exposure of the consumer is limited. However, this does not exclude the possibility of undiscovered pollution of local wells that can result in significant exposure of the local inhabitants.

It must therefore generally be assumed that drinking water meets current limit values, which state that the content of individual pesticide residues must not exceed 0.1 microgramme per litre, while the total content of pesticides must not exceed 0.5 microgrammes per litre.

With a normal consumption of 2 litres of water per day, a consumer thus receives less than 0.2 microgrammes of an individual pesticide, and his or her total pesticide intake from drinking water is less than 1 microgramme per day.

When the estimated maximum intake from drinking water of 1 microgramme per day is compared with the estimated intake of approx. 190 microgramme per day from fruit and vegetables, it must be concluded that the intake from drinking water is generally negligible and disappears in the uncertainty that lies in the estimation of the intake from vegetable food products.

Overall assessment of intake from food products and drinking water

As will be seen from the foregoing review of the pesticide intake from the different types of food products and drinking water, the predominant sources of the general population’s exposure to pesticides are fruit and vegetables and cereals and cereal products, while the intake from drinking water, animal food products and fish is of no significance for the total exposure.

The total average exposure from the individual types of food product and drinking water is summed in table 6.5.

Table 6.5
Estimated average pesticide intake from Danish and imported food products (Büchert 1998).

As will be seen from the table, the total average intake is estimated to be approx. 200 microgrammes of pesticide per day, about 60% of which comes from imported products, and the remaining 40% from Danish products, including cereals.

Variation in daily intake of pesticides

A rough calculation can be made of the variation in the intake of pesticides. These calculated extremes must be treated with caution because a closer statistical calculation is expected in the future. The lowest intake of pesticides is among people who either have a very low consumption of vegetable food products or who base their consumption solely on untreated, possibly organic, products. On the high side, the extreme must be presumed to be a so-called vegan, who bases his or her entire energy consumption on traditionally cultivated fruit and vegetables. In all probability, there are not many 100% vegans – people who live exclusively on vegetable products. A vegetarian typically covers part of his or her energy need with dairy products and eggs. For this reason, there are no detailed data on the typical composition of such vegans’ diet, but a total intake of fruit and vegetables and cereals and cereal products of around 2½ kg per day must clearly be regarded as at the upper end of the real consumption. That corresponds to three times the average consumption on which the calculations of the average Dane’s intake of pesticides through their diet are based. Judged in this way, the extremes for pesticide intake are estimated to lie from a very low intake to about three times the calculated average intake, corresponding to 570 microgrammes per day. Although this is an estimated calculation of the upper limit, it accords well with the calculated intake for the 90% fractile of the population.

The intake in relation to ADI

The calculations also show that the average intake at individual substance level is typically about 1% or less of the acceptable daily intake (the ADI value) for the individual compounds. Even with big variations in food consumption, the intake thus lies below the acceptable levels. As shown in figure 6.4, there are seven pesticides with a residual content of more than 1% of the ADI value for the pesticide in question, while all the other pesticides lie below 1% of ADI (Büchert 1998). This figure does not necessarily show the seven most eaten types of pesticide residues, which is illustrated by the fact that according to the diet data used, more than 90% of the two pesticides ortho-phenylphenol and methidathion are received through citrus fruit. Citrus fruits are usually peeled before being eaten, and there are today experiments that show that methidathion in citrus fruits is reduced by 95% by peeling the fruit. That means that the figures for methidathion, and presumably also for ortho-phenylphenol, can be more than 80% too high. Other pesticide residues are found mainly in crops that are not peeled or processed (e.g. cucumber, apples and pears), and the intake of these pesticides could in reality be more important than the real intake of the pesticides shown in figure 6.4. It must be stressed that it cannot be absolutely claimed that all calculations that do not include reduction factors are too high, since during preparation pesticides can be broken down into compounds that are just as harmful or more harmful than the original pesticide. However, it must generally be expected that including factors for processing/preparation of the crops in the calculations will reduce the value of the intake. In future, final and well-tested calculations that include reduction factors and that are supported by toxicological data will become available, making it possible to compare the intake of the different pesticides.

Figure 6.4 Look here!
The total average intake of pesticide residues (denoted I) from different fruit and vegetables, when account is not taken of such factors as peeling and similar that reduce the residual content of pesticides. The vertical line gives the mean value for all pesticides (0.3% of ADI).

Figure 6.5 shows the main crops shown by the calculations to contribute to the daily intake of pesticides. It should be noted that account is not taken of peeling and other factors that reduce the residual content of pesticides. Since citrus fruit is eaten without the peel, and apples are eaten with the peel, the real relationship between these two intakes could be rather different from this figure. Secondly, it should be noted that the figure does not say anything about the health effects associated with the different pesticide residues in the different crops. For example, it could be misleading to report that apples, for example, contribute most to the intake of pesticides if toxicologists have shown that the pesticide residues that apples contain are less harmful than other pesticide residues.

Figure 6.5
The total average intake of pesticide residues (denoted I) from different fruit and vegetables in microgramme per day. In the calculation, account has not been taken of peeling and other factors that may reduce the residual content of pesticides in the food products.

(Figure text:
Citrusfrugter = Citrus fruit
Æbler = Apples
Vindruer = Grapes
Bær = Berries
Andre frugter = Other fruit
Kartofler = Potatoes
Andre grøntsager = Other vegetables
fra xx pesticider = from xx pesticides

Uncertainties and reservations

It must be remembered that the calculations are encumbered with relatively great uncertainty. That applies to the determination of the residues of the individual pesticides and to the dietary data used. At the same time, the residues used are based on a cautious evaluation, which means that the values must be assumed to lie above the real content. The result is thus an over-estimation of the intake of both Danish and imported products. There is also a big variation in the data used for intake of diet. This variation is due partly to uncertainty in the determination of the mean intake of the individual food products and partly to a variation as a consequence of different eating habits in the population. Taken overall, the intake of the individual food products shown in table 6.5 can vary by several hundred per cent from one person to another.

However, it must be stressed that a person with a relatively large consumption of one type of food will often have a smaller consumption of other types, so variations in the total pesticide intake will not necessarily vary to the same extent as the food consumption.

6.2.5 Determination of the effects of pesticides on the population

Absorption and excretion of pesticides

Uptake of pesticides takes place after oral intake and, to a lesser extent, through inhalation or via the skin. Absorption via the lungs is normally fast compared with the other exposure routes because of the thin alveolar membrane and the ample blood flow. Absorption via the skin is often slow, but for pesticides that are metabolised quickly in the liver, skin exposure can be the main exposure pathway. With respect to exposure of the foetus, it has been found in animal studies that certain pesticides – particularly organophosphates and carbamats – can pass the placenta (Salama et al. 1993).

Metabolism

Metabolism or biotransformation of the absorbed, biologically available dose (the internal dose) determines how large a part reaches the target organ. Almost all the chemical changes that pesticides undergo in the body are due to special enzymes (Hayes, Laws 1991). The first stage in the biotransformation normally takes place via microsomal enzymes, which catalyse an oxidation or reduction reaction. These enzymes include all the cytochromal P450-enzyme systems in the liver, which is the main organ for biotransformation of chemicals. The degradation products are normally less toxic and more easily eliminated than the pesticide itself. However, for some pesticides, an activation takes place, which can lead to the formation of more toxic metabolites.

Bioaccumulation

Some pesticides that accumulate in the body’s fatty tissue have very long half-lives. These so-called persistent substances are now banned. They include the chlorinated pesticides, such as DDT and dieldrin.

Authorisation and risk assessment of pesticides with a view to public health

According to an EU directive (91/414/EEC) on marketing of plant protection products, a risk assessment of health and environmental properties of the product must be carried out in connection with the authorisation procedure. The magnitude of the real and the potential exposure must be determined, both for the users and for the consumers. Users should be understood to mean spraying personnel, workers and others who are exposed to the product during and after application. The consumers are exposed to the pesticides through food and drinking water or, for example, via soil pollution.

Limit values

Allocating limit values for content in food products is part of this authorisation procedure. If a substance can be authorised for use, a maximum limit value, MRL (Maximum Residue Limit), is fixed for the maximum residual content of the pesticide or its degradation or transformation products in food products.

The limit value in food products is based partly on a toxicological assessment of the health risk in connection with intake of the pesticide in question, with an Acceptable Daily Intake (ADI) being set and partly on the residual concentrations of the pesticide found in vegetable food products after use of Good Agricultural Practice (GAP). GAP means the nationally authorised methods of use that are necessary under current conditions for effective control of pests. To arrive at the maximum limit value, the health aspect (ADI) is combined with the use of the pesticide in question (GAP). This is done by combining ADI with the Theoretical Maximum Daily Intake (TMDI), calculated by means of diet models and assuming that all crops for which the pesticide may be used contain the maximum permissible amount of the pesticide. TMDI must lie below ADI for a limit value to be set. In Denmark, it is the Danish Veterinary & Food Administration that sets the limit values for food products.

Authorisation of pesticides

In connection with the authorisation procedure, not only the pesticide’s physical/chemical properties and its stability and degradation in nature must be tested, but also its toxic properties. There are internationally agreed guidelines for performance of the toxicological tests that are included in the risk assessment of pesticides. Both the active ingredient and the product must thus be tested for acute effects, and the active ingredient must be tested for chronic effects through repeated, long-term exposure (carcinogenicity, mutagenicity and effects on reproduction, including malformation of the offspring). In addition, tests are required concerning the substance’s absorption, metabolism, accumulation and elimination, together with any effect on enzymes and other biochemical parameters. In the toxicological testing of chemicals, account must be taken of the substance’s purity, stability in the exposure set-up and reproducibility in a possibly repeated test.

In the nature of things, most of the testing of the health effects of pesticides is done on animals (usually mice and rats) rather than people. There can be differences between test animals and humans with respect to metabolism, and far higher doses are normally used in the animal tests than the general population could be exposed to.

Acute reference dose

For certain pesticides, however, there is only a rather narrow margin between the doses that are acutely toxic and the doses that have long-term effects. For such pesticides, an acute reference dose is set in addition to the usual ADI as a protection against acute toxic effects. Readers are also referred to section 8.3 on the precautionary principle.

Measurement of the potential exposure

The potential human exposure to pesticides can be investigated by direct measurements in food products, drinking water or the environment. The most accurate data for exposure are presented in case reports, but only a group designation is usually used (e.g. insecticide, fungicide or herbicide) when describing the exposure, and the amount used is self-reported. In several studies of children and pesticides, the length of time the parents have been engaged in an occupation with potential pesticide exposure, for example, and the frequency and use of pesticides are used as indirect measures of the degree of exposure. Other studies have estimated the magnitude of the exposure by combining types of crops in an area with information about the use of pesticides that are specific to the crops in question. The rougher the measure used for classification of the type and extent of the exposure, the more likely it is that any real increased risk of health effects from specific pesticides will not be discovered.

The indicators can be too rough

In many of the studies, an assessment of effects is also often based on rough indicators. An exact description of the effects is extremely important but is often problematical – as in the case, for instance, of neurotoxic effects of pesticides, which can be very difficult to reveal and quantify. Assessments are frequently based on comparisons of mean values, whereby particularly deviant small groups can be overlooked. For cancer, tissue tests may be necessary in order to make specific cancer diagnoses. Sub-types of some diseases, e.g. leukaemia, can have different causes, and mixing these sub-types can blur a possible relationship with a given exposure. Owing to poor precision in assessment of both exposure and effect in the traditional epidemiology, incorrect classification is likely, which results in these methods having a low sensitivity, see below.

Epidemiological studies

Information on relationships between exposure to pesticides or other environmental factors and the occurrence of disease in humans is often obtained by means of epidemiological studies (also called population studies). Great caution must be exercised in interpreting the results of epidemiological studies because of a number of sources of error and inherent weaknesses in the different epidemiological models. It must be firmly stated from the start that epidemiological studies - in the classic sense – are not enough on their own to establish causal relationships.

The models comprise: 1) descriptive epidemiological studies (population-based) and 2) analytical epidemiological studies (individual-based).

Cross-sectional studies (descriptive studies)

In descriptive epidemiological studies, the lifestyle or conditions of life of groups (e.g. whole countries’ populations) are typically registered as causal factors. For example, the consumption of a given pesticide in different population groups can be compared with statistical data on morbidity and mortality in these population groups, or changes in the consumption of pesticides and morbidity or mortality over time in the same population group. An obvious drawback with descriptive studies is that it is not possible to make adjustment for known risk factors at individual level (e.g. smoking, obesity or alcohol consumption). In descriptive studies one can find certain patterns between exposure and disease. For example, a high consumption of pesticides and thus probably exposure to them in large, limited population groups (e.g. farmers) can be linked to an increased occurrence of cancer. However, such a relationship says nothing at all about causal relationships, i.e. that a high exposure to a pesticide cannot, from the above data, be said to be the cause of cancer but can give rise to a suspicion concerning causal relationships, which must then be examined more closely.

Analytical studies: case control studies

Case control studies are the most common type of analytical epidemiological studies. In these, one compares causal factors, e.g. lifestyle, in individuals with a given disease or other factor that one wishes to investigate, with healthy persons. The individual in the control group should be chosen at random, and with the same inclusion and exclusion criteria, from the same population base as cases. Case control studies are retrospective. Memory therefore plays a vital role. It is also the case that precisely the memory of a sick person is often seriously affected by the disease and can give rise to systematic errors (bias). It is also often uncertain which period of the sick person’s life is most relevant for the study. The longer the time elapsing between a harmful effect and the occurrence of recognised disease, the greater this problem becomes. A study that compares the pesticide intake through diet in women that have borne a child with a congenital defect with the intake in women that have born healthy children is an example of a case control study that is encumbered with these possibilities of error.

Analytical studies: cohorts

Another frequently used analytical epidemiological study – the prospective cohort study – has fewer weaknesses than case control studies. In the prospective cohort study, relevant information is gathered from healthy persons, who are then monitored for a period – often a number of years – during which the morbidity of the cohort is recorded. This means that when a disease occurs one has the possibility of going back and finding the factors that characterised persons that later became ill for comparison with persons that did not do so. In cohort studies one also has the possibility of extracting and storing biological material for later analysis. For example, analyses of blood samples, fatty tissue samples and milk from nursing mothers provide information about the exposure to pesticides.

Cohort studies have the major drawback that they require many participants because the incidence (number of new cases per year) of ordinary diseases (e.g. cancer) is relatively low. Another factor is that it can take a long time for a disease to develop. In the case of cancer, 20 years or more can elapse from the initiation phase until clinical diagnosis (see later). These factors mean that cohort studies are considerably more costly and more difficult to handle than case control studies.

However, in the case of cohort studies as well, it is not possible to determine whether there is a causal relationship. Persons with a high exposure to a pesticide probably differ in other ways from persons characterised by a low exposure. In studies, one often adjusts statistically for factors that can confound the result, e.g. socioeconomic status, smoking habits, alcohol consumption, physical activity, use of hormones, etc. These factors are called "confounders" or confounding factors. However, it is important to be aware that differences in, say, lifestyle and conditions of life cover a very large number of factors and too little is known about their effect on the development of disease.

Other sources of error

Lack of big differences in exposure in the population group studied can be a problem in studies of the effect of pesticides on public health. The sources of error mentioned above are just a few of the inherent sources of error in epidemiological studies. The uncertainty concerning, for example, intake of pesticides is a particular problem when there is only a small variation in intake in the population group studied. While the true difference in risk of, say, cancer between a lower and upper level of a narrow intake interval is probably small, the observed difference decreases with increasing uncertainty of the analytical measurements. A negative result, i.e. a lack of relationship between exposure to a pesticide and the risk of disease can therefore not be taken to mean that such a relationship does not exist.

For a more detailed discussion of confounding and other sources of error in epidemiological intake/exposure studies, see Tarasuk, Brooker 1997.

No conclusive evidence

It cannot be proven on the basis of epidemiological studies that pesticides, in the quantities to which the general population is exposed, for example, via diet, are harmful to health. Conversely, one can never completely prove scientifically that a pesticide cannot cause a health risk. One can, however, show, with greater or lesser (un)certainty, the probability or lack of probability of a health risk. This applies to all scientific work, including tests carried out on animals.

Low-dose exposure implies lengthy, continued or occasional exposure to low levels of pesticides. With this form of exposure the body slowly accumulates a quantity of one or more pesticides that is sufficient to produce undesirable effects in the body. Unlike the health effects of occupational exposure to pesticides (see section 6.1), there are very few epidemiological studies of the relationship between exposure of the general population and the risk of developing a disease. In the following, we sum up the findings from existing studies of the effect of pesticides on reproduction, the hormonal system, cancer, the nervous system and the immune system. For further amplification of the existing knowledge, readers are referred to Skadhauge (1998).

Reproductive toxicity

Toxic effects on reproduction can take the form of difficulty in conceiving (reduced fertility or unrecognised early miscarriage), infertility, miscarriage and stillbirth (Smith et al. 1997). In women, the effects can also manifest themselves in the form of paramenia (as a consequence of changes in the neuro-endocrine function in the hypothalamus, the pituitary gland and the ovaries) and, in men, in the form of a low sperm count or changes in the mobility or appearance of the sperm.

In animal tests, several pesticides have shown toxic effects on reproduction (Traina et al. 1994). Particular attention has been paid to pesticides with hormone-like() effects, but, in animal tests, a number of other chemical substances have proved able to affect the reproductive system, resulting in, for example, reduced quality of semen and infertility without it being possible to point directly to an oestrogenous effect. As stated earlier, several studies of individuals with a high occupational exposure have shown negative effects on the reproductive system and particularly on fertility. However, in the case of the general population, the data are much less certain.

In 1995, DEPA published a report that concluded that sperm quality in otherwise healthy men had been falling since the end of the 1930s (DEPA 1995a). In the same period, a marked increase in testicular cancer was recorded, particularly in younger men. An increased frequency of certain deformities of the sexual organs of boys also seemed to have occurred. However, there was insufficient documentation to determine whether (early) exposure to pesticides could have been a cause of these effects on the reproductive system. In the case of most chemical pollutants in our environment, it is unknown 1) whether they have an oestrogenous effect or not, 2) how big their effect is, individually or combined, and 3) the actual magnitude of the exposure (Editorial 1995).

Cancer

For a number of pesticides previously in use there is evidence of carcinogenicity in animals, whereas arsenic and mixtures containing arsenic are the only pesticides classified by IARC (International Agency for Research on Cancer) for which there is sufficient evidence of carcinogenicity in humans, based on an increased risk of lung cancer and skin cancer.

There are currently some few pesticides on the market that are classified as carcinogenic in group 3 (Carc 3), see section 8.1 and Lindhart et al. (1998).

Mechanism behind the development of cancer

The carcinogenic effect can be exercised in different ways. Some pesticides affect the cells’ DNA and, in the worst scenario, induce precisely the changes that enable the cells to develop malignant properties (initiators). Other pesticides can cause cancer to develop by stimulating initiated cells to divide further (promotors). In relation to pesticides, attention has been paid particularly to their hormone-like effect, since oestrogens, for example, can promote hormone-dependent initiated cells (e.g. mammary gland cells). However, pesticides may also affect the development of cancer in other and more indirect ways, for example by inhibiting specific parts of the immune system.

Cancer cannot be predicted

One big difficulty in investigating a relationship between exposure to an environmental factor and the risk of cancer is that cancer often takes a very long time to develop – up to 20 years and perhaps even longer. Despite intensive research, valid biomarkers for early stages of cancer have not been identified with certainty.

Findings in epidemiological studies

There are only a few epidemiological studies of the relationship between the risk of cancer and exposure to pesticides in the general population. Most of the studies have focused on the relationship between the level of organochlorine compounds in the blood and the risk of breast cancer. In 1993, a study from New York aroused some interest (Wolf et al. 1993). In this study, an approximately 4 times higher frequency of breast cancer was found in women with a high blood concentration of DDE and PCB. Dieldrin was not measured. In 1994, a similar study was carried out in California, and there, the relationship was not nearly as strong, even though the exposure to DDT was considerably greater (Krieger et al. 1994). A third major American study was unable to establish any relationship between the blood content of organochlorine compounds and the risk of breast cancer. However, the follow-up period was short, and problems with confounder correction resulted in statistical weakness (Hunter et al. 1997). Lastly, a recently published Danish study showed a statistically significant dose-related correlation between the blood content of dieldrin and the risk of breast cancer (Høyer et al. 1998). The other relationships between risk of cancer and blood content of beta-hexachlorocyclohexane, DDT and PCB were not statistically significant.

Relationship between pesticides and cancer not documented

As the results of the above-mentioned epidemiological studies indicate, there are data that show that exposure to organochlorine compounds can be connected with an increased risk of breast cancer, although without sufficient, clear grounds to deduce the significance for the general population. A scientific panel appointed by the National Cancer Institute of Canada came to a similar conclusion in a review of studies of mainly occupational exposure and risk of cancer (Ritter 1997). The panel concluded that there was insufficient scientific evidence that pesticides contributed significantly to total cancer mortality.

Hormonal toxicity

It is well documented that a number of persistent chemicals can affect the endocrine system by affecting the hormones in the body that are responsible for maintaining homeostasis and regulating the developmental processes (Gray, Ostby 1998; Kavlock et al. 1996; Tilson, Kavlock 1997; Porter et al. 1993). Endocrine disruptors have been broadly defined as exogenous substances that disrupt production, release, transport, metabolism, sorption, action or elimination of the body’s natural hormones (Kavlock et al. 1996; Tilson, Kavlock 1997). Some of these substances can induce the cytochromal P450 systems in the liver. This can affect the metabolism of steroid hormones (including sex hormones) and thyroid hormones, whereby secondary effects can be induced in hormone-dependent organs.

However, too little is known about endocrine disruptors, and the designation has in some cases been used where the biological relationship is far from clarified. The suspicion about the very persistent substances DDT, DDE and PCB is warranted in view of the effects these substances have on wild animals (e.g. seals, otters and alligators). For the endocrine disruptors, too, there are problems in extrapolating from studies of test animals with relatively high exposures to the relatively low exposures that occur in the environment and the very small amounts that humans are exposed to. These endocrine disruptions cannot be demonstrated in present test systems, but work is going on under OECD to improve the test programme for new chemicals, so that animal tests are better able to document such effects.

Developmental toxicity

Developmental effects are effects that occur in the individual during development as a result of exposure prior to conception, in the foetal existence or postnatally until the individual is fully developed. The result of the developmental disturbances can be death, structural abnormalities, inhibited growth or functional disturbances. However, it is often difficult to determine whether miscarriage or stillbirth is due to reproductive or developmental effects.

There are too few studies on the relationship between exposure to pesticides and developmental effects. This also applies to the potential of pesticides and fertilisers in contaminated groundwater to produce reproductive and developmental toxic effects in humans.

Neurotoxicity

The term neurotoxicity is used to describe a substance’s potential to change the structure or function of the nervous system, defined by neurochemical, neuropathological organ changes, behaviour and specific psychological processes such as sense perception, learning and memory. Many of these disturbances can be directly measured with neurochemical, neurophysiological and neuropathological methods, whereas others can only be interpreted by looking at the behaviour. The action mechanism of many groups of pesticides – particularly the insecticides – the intended target of which is the peripheral nervous system, leads directly to consideration of their potential neurotoxicity, whereas the neurotoxic potential of other groups is less clear. Studies of neurotoxic effects are difficult to perform and interpret, for which reason there are very few conclusive studies.

Experimental studies have shown that the nervous system is more vulnerable to exposure to chemical substances during development than when it is fully developed. Animal tests have shown that neurotoxicity as a consequence of low-dose exposure to such pesticides as organophosphates, pyrethroids, DDT and paraquat during development of the brain can lead to irreversible changes in the adult brain and induce behavioural and cholinergic changes in the adult animal, whereas exposure of an adult to the same substance has little or no effect (Eriksson 1997; Williams et al. 1997). Exposure to chemical substances during development of the nervous system can vary, both qualitatively and quantitatively, depending on the phase of development of the nervous system (non-linear dose-response curve). It can therefore be difficult to assess the effects of long term low-dose exposure on the basis of short-term studies. In addition, the development of the nervous system depends on the endocrine systems, which are responsible for sexual development and growth and are closely associated with the presence of circulating thyroid hormones. Moderate to major changes in the concentration of thyroid hormone during development result in motoric dysfunction, cognitive defects and other neurological abnormalities (Porterfield, Hendrich 1993). As stated, it can be difficult to assess neurotoxic effects. The National Research Council (1993) found that the present strategy for testing toxicity was inadequate for assessing toxicity to several organ systems, including neurological development processes.

In several epidemiological studies, Parkinson’s disease has been linked to pesticide use (including Semchuk et al. 1992). The main suspect was paraquat, the chemical structure of which is somewhat similar to a chemical (MPTP), which can induce parkinsonian symptoms in laboratory animals. There are no studies specifically elucidating the effect of paraquat.

Neurotoxicity in children

There are very few studies of children and neurotoxic effects as a consequence of exposure to pesticides, and clear conclusions cannot be drawn from them. There seems to be insufficient documentation of neurotoxic effects in the fully developed nervous system as a consequence of low-dose exposure to pesticides. However, experimental data provide a basis for assuming that the nervous system is vulnerable to pesticide exposure during development, partly due to disruption of endocrine systems, which are of importance for normal development of the nervous system.

Immunotoxicity

The toxicological tests required as a minimum before a plant protection product can be authorised can to some extent show whether a chemical substance has a potential immunotoxic effect when the organism is exposed to it. However, the test methods have some constraints, particularly with respect to sensitivity, i.e. their ability to show any weak immunotoxic effects. Generally speaking, chemical substances with a clear immunotoxic effect, including pesticides, will be identified in the required toxicological tests, whereas there can be a problem with substances with a medium to weak effect.

Immunotoxic effects of chemical substances, including pesticides, can occur as a consequence of the immune system being either weakened or strengthened, or if the immune system responds to the chemical substance as an antigen, which can lead to allergy or autoimmunity.

Several animal studies have shown immunological changes after acute or chronic exposure to pesticides (Banerjee et al. 1996; WHO 1996). In many cases, the results from these studies are difficult to interpret, and some of the studies could indicate that the immunotoxic effect can be a consequence of another, systemic, toxic effect. However, the tests show that pesticides, as well as other chemical substances, can have a potential effect on the organism’s immune system (WHO 1996).

Animal tests using rodents indicate that the immune system in the developing organism is more vulnerable than the fully developed organism. Experimental and clinical data from the working environment have also shown that chemical substances, including certain pesticides (chlornitrobenzene, captan og organophosphates) can induce contact hypersensitivity (type IV reaction) in test animals and humans (Cronin 1980).

The epidemiological evidence of immunotoxic effects as a consequence of exposure to pesticides is sparse. Immediate reactions (type I reaction) are thus only described in a few case reports that have been difficult to confirm (Baker, Wilkinson 1990).

Data from studies of chemical substances, including certain pesticides, show that these can affect the immune system under special experimental conditions. The tests on which the toxicological assessment is usually based can identify the pesticides that have a potential serious effect on the immune system. With the exception of contact hypersensitivity as a consequence of occupational exposure to pesticides, there are insufficient data to conclude that exposure to pesticides in the environment in normal circumstances will cause damage to health in the general population as a consequence of an effect on the immune system (Baker, Wilkinson 1990; Banerjee et al. 1996; WHO 1996).

6.2.7 Conclusions

There is insufficient epidemiological evidence to either prove or disprove a relationship between health effects and long-term low-dose exposure to pesticides. There are several reasons why there are considerable difficulties in gaining more certain knowledge about the effect of pesticides on human health. The epidemiological studies concerning the effects on humans of exposure to pesticides are characterised by imprecise measures for both exposure and effect, a relatively short follow-up period and lack of control of confounding factors. Due to limited group sizes, data are often collected in large groups, which further reduces the sensitivity. Owing to low exposure contrast and many confounding factors, there are often problems in proving any effects.

The following specific conclusions can be drawn:

For a relationship to be demonstrated epidemiologically, better measures are needed for both exposure and effect. The development of biomarkers may be a step in this direction.

It is important to constantly update the test methods for animal tests based on scientific development on the basis of experience in humans.

The review of the pesticide intake from food products and drinking water shows that the main sources of the population’s exposure is the intake from berries, fruit and vegetables and, to some extent, cereals and cereal products, while the intake from drinking water, animal food products and fish is of no significance to the total exposure.

The total average load from food products is estimated to be approx. 200 microgrammes pesticide per day, more than half of which comes from just a few types of food products, namely citrus fruit, potatoes and apples. Around 60% come from imported products and 40% from Danish products. There are big variations in the calculated numerical values, and, in practice, the total intake is believed to range between a very low intake and about 600 microgrammes per day. Since most of the pesticide residues in citrus fruits are in the peel, which is not eaten, the actual daily intake of pesticides is less than 200 microgrammes per day. In the last-mentioned scenario, the intake via Danish products would be greater than 50% of the total intake.

In treated crops it is assumed that there is generally some residual content of pesticides that decreases the longer the time that elapses between spraying and harvesting. This is, however, a factor that is particularly important if the pesticide is applied on crops or parts of plants that are edible at the time of harvest, i.e. after the end of flowering, seeding and similar. However, in farming practice, there are a number of other factors that influence the pesticide content of the crop. This applies not only to the plant’s development stage at the time of treatment but also to the concentration used, the method of application, etc. However, failure to detect residues does not mean that the crop is free of pesticides, but rather that the content is below the analytical detection level.

Residual content in harvested crops usually comes from pesticides applied at times and in forms of treatment in which the spray product is applied directly on plants in their seed-bearing, berry-bearing or fruit-bearing growth stages. The residual content in vegetable food products with high residual concentration levels could therefore be reduced by use of longer intervals between spraying and harvest, including restricting spraying to before the end of flowering, earing or similar.

The average load at single substance level is typically about 1% or less of the Acceptable Daily Intake (the ADI value) fixed on a mainly experimental, toxicological basis, where the safety margin between average human exposure and zero-effect level for the most sensitive effect in the most sensitive of the existing test systems is more than 1000.

The safety margin in the use of pesticides is based mainly on animal tests, since the safety margin with lifetime, low-dose exposure cannot, for ethical or practical reasons, be established on the basis of human tests.

The discovery of new effects that have not previously been studied or to which importance has not previously been attached, e.g. effects on the endocrine system and the nervous system during development, illustrates the importance of constant research. For example, the existing animals tests for authorisation of pesticides need improving with respect to detection of endocrine disruptors.

Differences in sensitivity between animals and humans and between one human and another make it necessary to use (un)certainty factors when ADI has to be fixed on the basis of data.

As a consequence of the aforementioned difficulties in carrying out long-term epidemiological studies of the effects of low-dose exposure, consideration could, however, be given to concentrating the research on areas in which deficient documentation should suggest caution, e.g. the possible need to introduce an extra uncertainty factor in order to protect children in cases in which there is insufficient toxicological information.

Risk assessment of the coformulants, considerable quantities of which are often used, should receive more attention in the assessment of the individual pesticide products, and the appropriateness of using the individual substances should be regularly reviewed.

For degradation products of pesticides in the environment, knowledge is lacking in some cases about their health effects. This applies particularly if other metabolites are formed in the environment than in test animals and humans.

In the health assessment, particularly for the risk groups (children and pregnant women) greater attention should be paid to the fact that many different chemical substances are taken in at the same time.

It cannot be proven on the basis of epidemiological studies that pesticides, in the quantities to which the general population is exposed, for example, via diet, are harmful to health. Conversely, one can never completely prove scientifically that a pesticide cannot cause a health risk. One can, however, show, with greater or lesser (un)certainty, the probability or lack of probability of a health risk. This applies to all scientific work, including tests carried out on animals. Furthermore, every statement about safety in connection with the use of chemical substances is based on the existing body of knowledge, so there is always the possibility of later findings with now unforeseeable effects.

The epidemiological studies of effects on humans of exposure to pesticides are characterised by imprecise measures for both exposure and effect, short follow-up times and lack of confounder control. In addition, limited group sizes mean that data are often pooled, whereby the sensitivity is further reduced.

There are practically no epidemiological studies of effects of metabolites that are formed in the environment.

In epidemiological studies, insufficient attention is paid to coformulants.

6.3 Poisoning caused by pesticides

The National Board of Health has carried out a study of hospital admissions, outpatient attendance and deaths in Denmark caused by pesticides in the period 1987-1996, using data from the National Registry of Patients and the Cause of Death Registry. However, the admission figures from the period before 1994 are encumbered with incorrect diagnostic codes (Skadhauge 1998). In the period 1994-1996, there were 88 admissions in all. Of these, 48% were children under the age of 11 years and 39% were women. With respect to outpatients, the first countrywide records are from 1995. 127 cases were recorded in 1951 and 51 in 1996. However, some of the codings in 1995 could be incorrect diagnostic codes. A manual examination of death certificates revealed 48 deaths, 45 of which were suicide and three accidents in children. For the admissions and outpatient cases, it is not possible to determine whether the poisoning occurred in connection with work in farming. The three child deaths all occurred in rural communities. Two of the cases were due to unlawful storage in unmarked packaging.

The Poisons Information Office of the Occupational and Environmental Medicine Clinic at Bispebjerg Hospital received 163 calls about pesticide poisoning in 1997. 47% concerned children aged 0-14 years. The calls covered the following groups of substances:

Some of the calls concerned parathion, which has not been used professionally for many years. In two thirds of the cases, the accident occurred in the home or garden, 12% occurred within farming and 5% in forestry undertakings or market gardens. However, it must be stressed that the figures cannot be regarded as representative, since the calls constitute only a small proportion of the events actually occurring.

6.3.1 Conclusions

A relatively large number of cases of pesticide poisoning are recorded each year. Deaths have occurred through suicide and accidents among children. About half the recorded admissions in connection with pesticide poisoning relate to children.

Cases of poisoning with pesticides that have been out of use for many years still occur.

6.4 The sub-committee’s conclusions and recommendations

The sub-committee deems the risk of acute effects from pesticides to be considerably lower today than it was just 10 years ago because the most harmful products are no longer permitted. The possibility cannot be excluded of some risk to persons who do not observe the given rules for personal protection and correct use of the pesticides, inappropriate work routines and poor work hygiene. However, the sub-committee notes that there can be considerable exposure of the sprayer operator and of workers in greenhouses and in the production of fruit and vegetables, where frequent use is made of pesticides.

The sub-committee concludes that the risk of occupational accidents in connection with mechanical weed control could rise with the introduction of more machines, which require repair and maintenance. Furthermore, increased manual weeding could result in more cases of injury due to repetitive, monotonous work (RMW). There is a generally increased risk of physical problems – particularly osteoarthritis – among workers in farming due to stable work, milking, tractor operation and heavy physical work, which are not related to the use of pesticides.

The review of the pesticide intake from food products and drinking water shows that the main sources of the population’s exposure is the intake from berries, fruit and vegetables and, to some extent, cereals and cereal products, while the intake from drinking water, animal food products and fish is of no significance to the total exposure.

Treated crops must always be assumed to have a certain residual content, so failure to detect a content can only be taken to mean that the content is in such case below the analytical detection level.

Limiting permission to spray after flowering or seeding would reduce the residual contents.

The total average load from food products is estimated to be approx. 200 microgrammes pesticide per day, more than half of which comes from just a few types of food products, namely citrus fruit, potatoes and apples. Around 60% come from imported products and 40% from Danish products. There are big variations in the calculated numerical values, and, in practice, the total intake is believed to range between a very low intake and about 600 microgrammes per day. Since most of the pesticide residues in citrus fruits are in the peel, which is not eaten, the actual daily intake of pesticides is less than 200 microgrammes per day. In this estimate, the intake via Danish products would be more than 50% of the total intake.

The average intake at single-substance level from food products is typically around 1% or less of the present Acceptable Daily Intake (the ADI value).

It cannot be proven on the basis of epidemiological studies that pesticides, in the quantities to which the general population is exposed, for example, via diet, are harmful to health. Conversely, one can never completely prove scientifically that a pesticide cannot cause a health risk. One can, however, show, with greater or lesser (un)certainty, the probability or lack of probability of a health risk. This applies to all scientific work, including tests carried out on animals. Furthermore, every statement about safety in connection with the use of chemical substances is based on the existing body of knowledge, so there is always the possibility of later findings with now unforeseeable effects.

Epidemiological studies of effects of metabolites and inert substances, which often make up a large part of the products, are largely non-existent.

6.4.1 The sub-committee’s recommendations

In both conventional and organic farming, farmers and workers are unaccustomed to thinking about health and safety, and not all injuries are reported despite the fact that there are many serious accidents in farming and more fatal accidents than in any other occupation. The sub-committee recommends that health and safety be given greater priority in both conventional and organic farming.

The sub-committee finds that too little is known about the ability of pesticides and their coformulants to produce allergies and about their effect on the immune system.

As a consequence of the intensive use of pesticides in nurseries and the production of fruit, vegetables and berries, the sub-committee recommends intensified action to reduce exposure to pesticides.

More extensive use of biomarkers for exposure to and the effects of pesticides would make it easier to demonstrate a relationship epidemiologically.

The discovery of new effects that have not previously been studied or paid much attention, such as effects on the endocrine system (hormones) and the nervous system during development shows the importance of constant research in these areas.

In the health assessment of pesticides, particularly with respect to risk groups, greater account should be taken of the fact that many different chemical substances are taken in at the same time.

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