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Pesticides in the Diets of Infants and Children 7 Estimating Exposures THE TWO PRECEDING CHAPTERS have reviewed data on the diets of infants and children (Chapter 5) and on pesticide residues in food (Chapter 6). This chapter addresses methods for estimating ingestion of pesticides by infants and children using the data from the preceding two chapters. Although nondietary sources of pesticide exposures such as air, soil, and consumer products are also considered, emphasis is placed on the ingestion of pesticide residues present on foods consumed by infants and children. Dietary exposure to pesticides depends both on food consumption patterns (Chapter 5) and on residue levels on food (Chapter 6). Multiplying the average consumption of a particular food by the average residue of a particular pesticide on that food yields the average level of ingestion of that pesticide from that one food commodity: Consumption x Residue = Dietary Exposure. In reality, however, estimation of dietary exposure to pesticides is more complex than this simplified equation. Since many pesticides are used on a number of food crops, determination of the total exposure to a pesticide must be based on consumption data for all such foods. Also, it may be of interest to consider the total ingestion of different pesticides such as organophosphates and carbamates that fall within related classes and may pose similar risks to health. The data presented in Chapter 5 indicate that food consumption levels vary both among and within individuals. This variation can be represented in terms of a distribution of food consumption, reflecting both high
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Pesticides in the Diets of Infants and Children and low consumption levels, as well as the average level of consumption. Pesticide residue levels present in food will also vary, depending on several variables including application practices in different regions, time that has elapsed since application, degradation during transportation and storage of food, and the manner in which food is prepared by the consumer. Thus, both food consumption and pesticide residue data are characterized not by a single value but, rather, by a broad distribution reflecting high, low, and average values. The variation in food consumption and residue data produces considerable variation in dietary exposure of pesticides by infants and children. This can be represented by a distribution of exposures across individuals within a particular age group. The distribution of dietary exposures is determined by the distribution of food consumption levels and the distribution of pesticide residues in food. If both the distribution of food consumption and the distribution of residue levels are known, statistical methods can be used to infer the distribution of dietary exposures. The process for combining different distributions into one distribution is termed convolution. The statistical convolution methods that can be used for this purpose are discussed later in this chapter. Since ingestion of pesticides is dependent upon both food consumption and pesticide residue levels in food, it follows that the quality of dietary exposure data is determined by the quality of consumption and residue data. Although food consumption surveys such as the Nationwide Food Consumption Survey (NFCS) provide data on consumption patterns in the population at large, these surveys have generally not targeted infants and children. Hence, they included relatively small sample sizes within the age groups of primary interest for this report. One exception is the 1985–1986 Continuing Surveys of Food Intakes of Individuals (CSFII), which did focus on food consumption patterns of children. Determination of the distribution of pesticide residues in foods consumed by infants and children is also difficult: only a fraction of all food consumed can be tested for the presence of pesticide residues. Many of the available residue data are based on surveillance studies that because of their focus on potential problem areas may overstate residue levels in the general food supply. The detection limit of residue monitoring methods can also impart uncertainty as to the residue levels actually present on food, especially when many residues are below the limit of detection and the detection limit is relatively high. Recognizing these data limitations, the committee has included in this chapter several examples to illustrate possible approaches to estimating the distribution of dietary exposure to pesticides for infants and children. Each of these examples is designed to illustrate different aspects of exposure estimation, including the estimation of average daily exposures for use in chronic toxicity risk assessment and the estimation of peak exposures
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Pesticides in the Diets of Infants and Children for evaluating acute toxic effects. Examples are included to illustrate how total exposure to pesticides used on more than one food crop can be estimated, and how exposures from different pesticides falling within the same toxicological class can be combined based on their relative toxicity. Because of the limitations in the available consumption and residue data, it must be stressed that the purpose of the examples is to identify methods for estimating exposure and not to produce representative estimates of actual exposure. The particular compounds chosen for study were selected data were available to illustrate the approaches to exposure estimation considered by the committee. All results should be taken in the context of the limitations of the data as described in this and the previous two chapters. Application of these methods in a regulatory context will be possible only if adequate data on the distribution of both food consumption and pesticide residues in food can be obtained. The first example deals with benomyl, a systematic fungicide that has not been permitted for postharvest use in the United States since 1989. Because of the chronic toxic effects of this compound (benomyl has been shown to cause malignant liver tumors in mice), the average daily ingestion of benomyl was considered to be most relevant for estimating long-term exposure. Note that although the focus is on the average daily ingestion by individuals over an extended period, the daily ingestion will vary from person to person, depending on their food consumption habits and the residues of benomyl in the foods consumed by each person. Since residue data were available for apples, grapes, oranges, peaches, and tomatoes, this example was used to illustrate the estimation of total exposure to a single pesticide from multiple food commodities. Data on benomyl from different residue monitoring programs were available to the committee, permitting a comparison of exposure estimates based on different residue data. For example, field trial data derived from pesticide analysis in the manufacturer's laboratory (using a special method not adapted to multiresidue screening) usually show higher detection rates than those found by government agencies in random sampling of food shipments. Field trial data are useful only as estimates of maximum residue concentrations from field test plot trials at treatment levels proposed for registration purposes. Because field tests are generally conducted at the maximum pesticide use allowed in its registration, the residue concentrations are often higher than those found in random sampling. The results of field trials are generally used to establish farm tolerances and analytical methodology for purposes of registration. Further evaluation of field trial data is required in order to evaluate pesticide degradation following application. The impact of residue data below the limit of quantification (LOQ), a
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Pesticides in the Diets of Infants and Children concentration below which residues cannot be accurately measured, was also investigated in this example. For nondetectable residues, it is possible that the actual (unknown) residue could be as low as zero or as high as the LOQ itself. The limitation of data on actual residue concentrations below the LOQ imparts additional uncertainty about the level of exposure to infants and children. Aldicarb is the subject of the second example. This acutely toxic pesticide exerts its effects by inhibiting cholinesterase enzymes in the nervous system. The example focuses on dietary exposure to aldicarb first from potatoes and bananas separately and then from potatoes and bananas combined. It serves to illustrate how estimates of exposure to a single pesticide found on more than one food can be derived. In contrast to benomyl, where average daily exposures are of interest, individual daily intakes are examined in this example because of the acute toxicity of aldicarb. Part of the aldicarb residue data is derived from composite sampling, which may underestimate peak residues found in individual potatoes or bananas as a consequence of compositing prior to residue analysis. Composite samples are not very satisfactory in acute risk assessment for raw food commodities like potatoes and bananas. However, residue levels in processed foods can be estimated by using composite samples. The third example addresses methods for estimating exposure to a class of pesticides inducing a common toxic effect. Specifically, the committee considered five organophosphate compounds used on different fruits and vegetables. All these compounds can inhibit plasma cholinesterase. A measure of total exposure to all five organophosphates is proposed based on their relative potencies. Before these short examples are presented, there is a discussion of statistical methods for combining the distribution of food consumption with the distribution of residue levels in food to arrive at a distribution of dietary exposures based on the method of convolution. The chapter concludes with a brief summary of nondietary sources of exposure to pesticides. THE USED OF FOOD CONSUMPTION AND RESIDUE DATA FOR EXPOSURE ASSESSMENT Food Consumption Data The most appropriate dietary exposure data for risk assessment depends on the nature of the adverse health effects of concern. In the absence of specific dose-response effects, the average level of exposure of an individual over a certain period provides a reasonable measure on which to
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Pesticides in the Diets of Infants and Children base estimates of chronic toxic effects such as cancer. For acute toxic effects, peak exposures over shorter periods are more appropriate for risk assessment. Average Levels of Consumption The development of food consumption data for evaluating chronic toxicity requires careful consideration. In general, food consumption surveys yield data on the consumption of that food over all days for which data are available. The average daily consumption for children within a given age class is then obtained by averaging across all the individuals in the age class. Estimating the average daily consumption of a particular food within a given class warrants some discussion. Since some foods will not be consumed at all by some individuals, estimates of average daily consumption based on all individuals in the sample will underestimate average consumption for the subpopulation of individuals who consume the food in question. For this reason, separate estimates of average daily consumption for "all children" and for "eaters only" are considered when estimating exposure. Average consumption levels for "eaters only'' are typically 2 to 3 times higher than those for "all children." Because food consumption data are available for only a few days each year, the proportion of children falling into the eaters-only group is underestimated. This problem is accentuated if only a 24-hour recall or 24-hour food record is used. If food consumption data were available for every day of the year, more children who consume the food of interest on an infrequent basis would be included in the eaters-only group. Thus, since the eaters-only group omits some individuals whose consumption levels are low, the average food consumption for "eaters only" calculated in this way actually overestimates the average consumption for this group. This bias does not occur when information on food consumption is obtained through food frequency questionnaires rather than 24-hour recalls or 24-hour food diaries, since food frequency tables in principle accurately identify those individuals who consume the food at any time during a given year. Scientists working with food consumption data have long recognized that consumption by a "typical" individual will not be representative of consumption by people who eat large amounts of a particular food. This has stimulated interest in examining the distribution of average daily consumption levels across individuals in order to estimate consumption by individuals who consistently consume greater quantities of the food of interest than the average. This distribution of average daily consumption across individuals can be used to estimate upper quantiles of consumption,
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Pesticides in the Diets of Infants and Children such as the 90th, 95th, or 99th percentile. Reliable estimates of extreme percentiles can, however, be obtained only with relatively large sample sizes. Because the distribution of average daily intakes based on a sample of food consumption records for several days includes variability both between children and among days within children, this distribution will be subject to greater dispersion than would be the case if day-to-day variability were eliminated. (In the ideal case, this could be achieved by monitoring food consumption data over a full year or by using food frequency questionnaires.) The implication of such overdispersion is that upper percentiles of consumption will be overestimated. Peak Levels of Consumption Although the average level of individual exposure to pesticide residues in food is an important determinant of chronic toxicity, peak levels of exposure are more relevant for evaluating acute toxicity. Episodes of relatively high exposure occurring in a single day or even during a single meal may be more pertinent for acute risk assessment, depending on the toxic effect of interest. The 1977–1978 NFCS provides information about food consumption during individual eating occasions for 3 different days. These data permit estimation of the total ingestion of a particular pesticide for each individual in the survey on each day. Using data for different individuals in the survey, one can estimate the distribution of person-days of consumption of specific foods. By combining this information with data on the distribution of pesticide residues in the food product or products of interest, it is then possible to estimate the number of person-days each year during which exposure to pesticides in the diet will exceed a critical level such as the reference dose (RfD), as defined in Chapter 8. Although average levels of consumption and exposure will be reasonably well estimated with this approach, upper percentiles will be underestimated since food consumption data are available for only 3 of the 365 days in a year that are of interest. This is in contrast to the case for chronic risk assessment, where upper percentiles of exposure are likely to be overestimated. Residue Monitoring The point at which food samples are taken will influence the residue levels found. The highest residue levels generally occur immediately following application, and are reflected in field trial data. In samples taken for surveillance or compliance purposes, the residues will generally be higher than those in samples randomly drawn from the entire stock of a
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Pesticides in the Diets of Infants and Children particular food commodity available for sale in a particular region of the country. Market basket surveys are based on a composite sample of a limited number of commonly consumed foods after they have been cooked or prepared for consumption in the usual manner. Although market basket surveys provide residue data under conditions designed to emulate foods as consumed, they are limited because they provide only composite sampling results on a few foods included in a typical meal. Most analytical methods for measuring pesticide residues in food are subject to an LOQ below which residue levels cannot be accurately determined. Although improved analytical methods for testing for pesticide residues in food have made it possible to detect lower and lower residue levels, even the most sensitive techniques are subject to an LOQ. When residue levels below the LOQ are reported, it is not possible to determine whether the food contains no residue of the pesticide of interest or whether there is a residue present but at a lower level than can be detected with the analytical methods used. This uncertainty about the actual residue level with residues below the LOQ confers uncertainty on the distribution of pesticide residues in food products and, subsequently, on the distribution of dietary exposure to pesticide residues by individuals consuming those foods. For example, consider a hypothetical distribution of residue levels based on the analysis of a number of food samples that may have been treated with a particular pesticide, as shown in Figure 7-1. The residues above the LOQ will generally follow a log-normal distribution. However, an appreciable proportion of the samples will produce results below the LOQ. What can be inferred about residue levels in samples below the LOQ? The only certain inference is that the actual residue level lies between a lower limit of zero and an upper limit equal to the LOQ. (Even this upper bound may not be entirely correct, since analytical results near the LOQ will be subject to some degree of measurement error.) Because not all crops grown in the United States are treated with pesticides approved for use on those crops, it is possible that results below the LOQ may be entirely pesticide free. Consider, for example, the data on the use of different pesticides approved for use on apples shown in Figure 7-2. The percentages of the U.S. apple crop treated with specific pesticides varies widely, ranging from a low of 1% for malathion to a high of 90% for azinphos-methyl. Thus, most apples will not contain residues of malathion and would produce residue levels below the LOQ when tested. It is also possible tests for azinophos could yield results generally below the LOQ if residues of this widely used pesticide were present at low but nondetectable levels. The data on pesticide use in Figure 7-2 also reveal marked regional differences in pesticide usage patterns in different regions of the country.
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Pesticides in the Diets of Infants and Children FIGURE 7-1 Hypothetical distribution of residue levels with a log-normal distribution for residues greater than zero. Captan, for example, is widely used on apples grown in the central, northeast, and northwest regions of the United States but is virtually unused in the western regions of the country. Variation between pesticide usage patterns in different countries also warrants consideration with regard to imported food products. In the past, results below the LOQ have been handled in different ways. A simple resolution of this uncertainty is to assume that all the results below the LOQ contain no residue and to assign them a residue level of zero. This is an optimistic approach, since the possibility of small but undetectable residues in some or all such samples cannot be excluded. A conservative approach is to assume that all residue levels are present at the LOQ. Although this may provide an upper bound on undetectable residues, it is unlikely that all the samples for which no residue was detected actually contain residues equal to the LOQ. An intermediate approach is to assume all nondetectable residues are present at one-half the LOQ. Clearly, the lower the LOQ, the less difference there will be between these different approaches, and the less uncertainty the LOQ will confer on estimates of potential human exposures.
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Pesticides in the Diets of Infants and Children Combining Residue and Exposure Data Variation in food consumption patterns and in levels of pesticide residues in food leads to variation in dietary exposure to pesticides among infants and children. This variation in the ingestion of pesticide residues is characterized by a distribution of exposures, reflecting high, low, and average exposure concentrations. Statistically, the distribution of exposures can be obtained by convoluting (i.e., combining) the distribution of food consumption with the distribution of pesticide residues in food (Feldman and Fox, 1991). Thus, once the food consumption and residue distributions have been determined, the distribution of dietary exposures can be calculated (Figure 7-3). The technical basis of convoluting two distributions can be described briefly as follows. Let C denote the consumption of a particular food by an individual, R the residue level in that food, and e the corresponding dietary intake or exposure level. The level of consumption will vary from person to person in accordance with the cumulative distribution FC(c) with corresponding density ƒC=F1. Note that FC(c) denotes the proportion FIGURE 7-2 In the 1990 apple crop, percent of apple production treated with the following chemicals: azinphos-methyl, benomyl, captan, cabaryl, malathion, and EBDCs.
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Pesticides in the Diets of Infants and Children FIGURE 7-3 Convolution of food consumption distributions and residue distributions to produce dietary exposure distributions. of the people in a given age group whose consumption C is less than a particular value c; the densities ƒC and ƒR reflect the relative frequency of different levels of consumption and residue, respectively, within the group. Letting FR denote the residue distribution with density ƒR=FR1, the distribution FE(e) of dietary intakes is defined by assuming that consumption C and residues R statistically independent (Feldman and Fox, 1991, p. 349). This relationship provides the technical basis for combining the consumption distribution FC with the residue distribution FR to obtain the exposure distribution FE. In practice, estimates of consumption and residue distributions are based on survey data and are represented as histograms based on the observe sample.(If different weights are attached to the survey observations, a weighted distribution should be used.) Computationally, these two distributions can then be convoluted simply by taking the result of each point from the consumption distribution and multiplying it by each point in the residue distribution; the distribution of dietary intakes is then defined by the distribution of these products. This empirical approach to convolution will work well, provided that the number of observations used to obtain the consumption and residue distributions is not large. With large distributions, the computation burden can be reduced by working with a random sample of both the consumption and residue data. The Monte Carlo approach (i.e., random sampling) to convolution was used by the committee in those examples where the computational effort required to convolute the two distributions was found to be excessive. The form of Monte Carlo sampling used by the committee was simply a means of reducing the amount of computational time required for convolution by using the original consumption and exposure distributions; no artificial distributional assumptions were required
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Pesticides in the Diets of Infants and Children to implement this technique. The Monte Carlo distribution of dietary exposures will converge to that based on the entire exposure distribution as the number of Monte Carlo samples increases. As the number of samples converge, the distributions become identical. The convolution method can be extended to more complex situations such as the estimation of total exposure to a pesticide that may be present on more than one food commodity. In this case, a single point on the exposure distribution is estimated by randomly combining points from the consumption distributions for all foods of interest with points from the corresponding residue distributions (one for each food), and then summing the total exposure across all foods. This process is repeated to generate a distribution of total exposures from all foods combined. Total exposure to pesticides within the same class can be estimated in a similar fashion using the relative potency values for those pesticides to express the intake in toxicity equivalence factors. This is illustrated in the example of organophosphate pesticides later in this chapter. LONG-TERM EXPOSURE TO BENOMYL The Compound Benomyl, or Benlate, is a systemic fungicide that was used in the United States from the time of its registration in 1972 until registration was voluntarily withdrawn for postharvest use by the manufacturer in 1989. Before then, it was the most widely used of the fungicides in the family of benzimidazole pesticides. Benomyl is effective in preventing more than 190 fungal diseases, and it acts as a protective surface barrier while also penetrating the plant tissue to arrest infections. It was applied as a seed treatment, a transplant dip, and a foliage spray and was registered for use on more than 70 crops in 50 countries, including imported foods such as bananas and pineapples. In the United States, more than 100 EPA tolerances were established for benomyl in a variety of foods and feeds. Benomyl has been shown to induce hepatocellular carcinomas, and combined hepatocellular neoplasms occurred in male and female mice treated with benomyl at all doses. In tests that included methyl-2-benzimidazole carbamate (MBC)—a metabolite of benomyl—investigators observed combined hepatocellular neoplasms in male mice and hepatocellular adenomas, carcinomas, and combined hepatocellular neoplasms in female mice (NRC, 1987). Because of its carcinogenic potential, exposure assessment for benomyl is based on the distribution of average ingestion levels for different individuals.
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Pesticides in the Diets of Infants and Children Playground Equipment Wooden playground equipment is another source of pesticide exposure because of the various kinds of wood preservatives used to prevent microbial and insect attacks. A 1987 California survey estimated that approximately 20% of all wooden structures in parks were treated with chemical preservatives. Some wood preservatives—PCP, chromium, boric acid, creosote, and arsenic—can induce adverse skin reactions such as contact dermatitis, hyperkeratosis, and, in the extreme case, skin cancer (CDHS, 1987). Exposure via Medications and Personal Products Another important route of exposure involves the direct application of insect repellents and pediculocides to children's skin. These include such compounds as N,N-diethyl-m-toluamide, lindane, and malathion. Lanolin, used by some breastfeeding mothers on their nipples, is also a concern because of the pesticides it can contain. N,N-Diethyl-m-toluamide N,N-Diethyl-m-toluamide, commonly called Deet, is the active ingredient in numerous commercially available insect repellents. Although insect repellents can provide great personal benefit, rare adverse reactions can occur. Since 1961, at least six cases of systemic toxic reactions from repeated cutaneous exposure to Deet have been reported. Six girls, ranging in age from 17 months to 8 years, developed behavioral changes, ataxia, encephalopathy, seizures, and/or coma after repeated cutaneous exposure to Deet ; three died (Oransky et al., 1989). Neurobehavioral analysis showed strong correlation between Deet exposure and affective symptoms, insomnia, muscle cramps, and urinary hesitation (McConnell et al., 1987). In August 1989 the New York State Department of Health investigated five reports of generalized seizures temporally associated with topical use of Deet. Four of the patients were boys from 3 to 7 years old (Oransky et al., 1989). Lindane and Malathion For almost 30 years the pesticide lindane (a chlorinated hydrocarbon) has been used in a shampoo for the treatment of head lice (Taplin and Meinking, 1988). Concern has been raised about potential central nervous
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Pesticides in the Diets of Infants and Children system damage from exposure to lindane. In particular, cases of central nervous system toxicity have been reported from accidental ingestion as well as from single percutaneous exposures (Lee and Groth, 1977). One author reported two instances in which lindane lotion was given orally to children with scabies because of a lack of communication in one case and a language barrier in the other (Taplin and Meinking, 1988). Malathion has been recommended as a preferable treatment over lindane (Taplin et al., 1982; Fine, 1983). Lanolin Lanolin, a derivative of sheep's wool, is commonly used as an ointment to treat sore, cracked skin. Mothers who breastfeed frequently use it on their nipples, and it is sometimes applied directly to children's skin. The organophosphate pesticides diazinon and chlorpyrifos and several organochlorine pesticides such as dieldrin have been found at measurable levels in lanolin. The U.S. Food and Drug Administration identified 16 pesticides in lanolin it sampled in 1988. The principal source of these residues is the wool from sheep treated with a pesticide dip to control parasite infestations in the fleece (Cade, 1989). The fat-soluble organophosphate pesticide diazinon presented the greatest concern because of its frequent occurrence (21 of 25 samples) and the high levels identified (up to 29.2 ppm). (T. Levine, EPA, personal commun., 1988). Occupational Exposures In agricultural communities, children are often directly exposed to pesticides when they accompany their parents in the field or work there themselves (Pollack et al., 1990). In 1980, some 19 farm workers suffered organophosphate poisoning after working in a cauliflower field (Whorton and Obrinsky, 1983). Five of the workers were 18 years old or younger; three of those were between the ages of 9 and 15 years. Exposure via Accidental Ingestion Accidental poisonings are all too common among children. In one study of 37 children who had been hospitalized at Children's Medical Center in Dallas as a result of organophosphate or carbamate pesticide poisoning, ingestion of a liquid was the most common (73%) mechanisms of exposure. Zwiener and Ginsburg (1988) reported that most poisonings took place in the home and here the result of careless storage of the original container or placement in unmarked or uncovered containers.
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Pesticides in the Diets of Infants and Children Conclusions and Recommendations Like other members of the general population, infants and children are exposed to pesticide residues in their diets. Estimation of dietary intakes requires information on both food consumption patterns and residue levels in food. The purpose of this chapter has been to demonstrate methods for estimating exposure to pesticides in the diet. The committee was guided by previous work on exposure estimation by the National Research Council (NRC, 1988, 1991a,b). Infants and children are also exposed to pesticides by nondietary routes, including air and contaminated surfaces such as rugs and playground equipment. Although a detailed analysis of nondietary routes of exposure to pesticides is outside the scope of this report, it is important for risk assessment purposes to consider the total exposure from all media. The following are the conclusions of the committee. Conclusions Pesticide residues are present in the diets of infants and children. Estimation dietary intakes of pesticides by infants and children requires information on both food consumption patterns and residue levels in food. Accurate estimation of dietary intake of pesticides by infants and children is difficult due to the limited amount of data on food consumption patterns of infants and children (Chapter 5) and limitations in the available data on pesticide residues (Chapter 6). Dietary exposures to pesticide residues can vary widely. Since most pesticide residues in foods are below the analytical limit of quantification, with comparatively few high residue levels, the distribution of dietary exposure to pesticides includes many low intakes. Some degree of positive skewness may be observed due to the occurrence of high consumption or high residue levels. To estimate dietary exposure to pesticides for infants and children, the committee combined probability distributions of food consumption with probability distributions of residue levels in order to obtain a probability distribution of individual exposures. The use of probability distributions for exposure assessment provides a more complete characterization of human exposure to pesticides residues in food than the use of summary statistics such as means or upper percentiles of exposure. More accurate estimates of upper quantiles of the exposure distribution
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Pesticides in the Diets of Infants and Children can be obtained by pointwise multiplication of the residue and consumption distributions than by multiplying the quantiles obtained from the residue and consumption distributions, separately. Moreover, the probability distribution approach based on 1-year age groupings of children provides useful information on differences in exposure patterns for children 1 to 5 years of age. Average daily ingestion of pesticide residues is an appropriate measure of exposure for chronic risk assessment, whereas actual individual daily ingestion is more appropriate for acute risk assessment. Since chronic toxicity is often related to long-term average exposure, the average daily dietary exposure to pesticide residues may be used as the basis for risk assessment with delayed irreversible chronic toxic effects. To take into account different food consumption patterns among individuals, the distribution of average daily dietary intake of pesticides should be examined within the population of interest. Since acute toxicity is more often mediated by peak exposures occurring within a short period (e.g., over the course of a day or even during a single eating occasion), individual daily intakes are of interest for risk assessment for acute toxic effects. Examination of the distribution of individual daily intakes for persons within the population of interest reflects both day-to-day variation in pesticide ingestion for specific individuals as well as variation among individuals. This distribution can be used to estimate the number of person-days in a given period during which intake will exceed a specified level, such as the acceptable daily intake (ADI), or reference dose. At present, there is a relatively limited amount of information on food consumption patterns of infants and children. To obtain accurate estimates of the distribution of individual intakes, more elaborate and more intensive consumption monitoring protocols are required. Because residue monitoring surveys conducted for compliance purposes are expected to lead to higher residue levels than those present in the general food supply, assessment of human exposure should normally be based on surveillance surveys. In using surveillance data, however, consideration needs to be given to regional differences in pesticide use and resultant residue levels. The committee acknowledges that pesticide food surveillance data are generated by randomly sampling food items from the distribution system. The purpose of this sampling is to ensure agricultural compliance with acceptable pesticide use practices. This sampling is broad-based and often not focused only on pesticides actually used. Pesticide field trial data are generated under strictly controlled conditions of use. These data better reflect actual levels at the time of harvest when it is known that a specific
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Pesticides in the Diets of Infants and Children pesticide has been used. Each data source is used for purposes other than identifying actual dietary exposures, although both are useful in attempting to estimate these exposures. Frequently, the levels of pesticide residue in foods are below the analytical limit of quantification (LOQ). Since the actual residue level in such cases may lie anywhere between zero and the LOQ, there is some uncertainty about actual exposures in such cases. For example, replacing the residue measurements below the LOQ with zero yields lower exposure estimates than substituting the LOQ for the unknown residue level. Notable differences occur when the analytical method is insensitive, the LOQ is high, or a large proportion of residues lies below the LOQ. The concentration of pesticide residues in foods may increase or decrease during food processing. Changes in residue levels that occur during the processing of food are especially important in assessing the exposures of infants and young children, who consume large quantities of single processed foods, such as fruit juices, milk, and infant formula. In addition to the data accumulated by the food industry (Chapter 6), studies by pesticide manufacturers such as those furnished to the committee on the fate of residues during processing need to be conducted for most pesticides that produce detectable residues in food. Specific pesticides can be applied to more than one crop and, hence, appear on a number of food commodities. Residues of several pesticides may also appear on a single food commodity. Intake of multiple pesticides with a common acute toxic effect can be estimated by converting residues for each chemical to equivalent units of one of the compounds. The standardized residues can then be summed to estimate total residue levels in toxicity equivalence factors, and then combined with consumption data to construct a probability distribution of total exposure to all pesticides having a common mechanism of action. Certain classes of pesticides such as cholinesterase inhibitors act by a common toxic mechanism. To properly evaluate the potential health effects of exposure to such pesticides, it is important to consider the total exposure to all pesticides in the class. Children are exposed to pesticides by nondietary routes. Occupational exposure of the parent could result in exposure of the child in utero, in the home environment, or in the occupational setting of the parents. Pesticide residues have been detected in outdoor and indoor air, on contaminated surfaces, and in medications and personal products.
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Pesticides in the Diets of Infants and Children When less than 100% of a given crop is treated with a particular pesticide, consideration might be given to adjusting exposure estimates according to the percentage of crop acreage treated. This adjustment can result in substantial reductions in estimates of exposure. This adjustment will be appropriate when the percentage of the crop treated is similar in different regions of the country, or when the crop is uniformly distributed throughout the country. Such adjustments should not be considered in the case of pesticides inducing acute toxic effects, since peak exposures are of importance in this case. When these adjustments are used to adjust national data, they may result in averages that do not account for regional differences in pesticide use. It is therefore important that exposure estimates that have not been adjusted for acreage treated be presented and that such adjustments be critically examined. Recommendations The following recommendations were developed by the committee. Probability distributions based on actual data rather than simple summary statistics such as means or percentiles should be used to characterize human exposure to pesticide residues on food. The advantage of using probability distributions rather than summary statistics to characterize exposure is that variation in individual food consumption patterns and residue levels in food are taken into account. This will require the collection of more detailed data on food consumption and residue levels as discussed in Chapters 5 and 6, respectively, but will provide more statistically robust estimates than the agency currently develops. The distribution of average daily exposure of individuals in the population of interest is recommended for use in chronic toxicity risk assessment; the distribution of individual daily exposures is recommended for evaluating acute toxic effects. This recommendation is based on the committee's observation that chronic toxicity is typically related to long-term average exposure, whereas acute toxicity is more often mediated by peak exposures occurring within a short period, either over the course of a day or even during a single meal. If appropriately designed and conducted, surveillance studies of pesticide residues in food provide unbiased data on residue levels in food products. Field trials are also useful sources of information on pesticide residues in food. Such studies should be continued in order to expand the data base for evaluating dietary exposures to pesticides.
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Pesticides in the Diets of Infants and Children Surveillance studies based on random samples designed to provide a representative picture of residue levels in food are required to obtain unbiased information on dietary exposure to pesticides. The committee recommends that research to reduce the uncertainty in estimates of dietary exposure to pesticides be encouraged. Specifically, the development of improved analytical methods for residue analyses and statistical methods for imputing residue levels below the LOQ can lead to improved estimates of pesticide exposure. All analytical methods for measuring pesticide residue levels in food are subject to an LOQ. Results below the LOQ may be as low as zero or as high as the LOQ itself, thereby imparting uncertainty regarding actual human exposure levels. This uncertainty will be reduced if more sensitive methods with lower LOQs are developed. Such technological improvements should be encouraged even in the absence of other pressures for more sensitive analytical methods. Statistical methods for use with censored data (i.e., based on specific assumptions) can be used to impute residue levels below the LOQ, provided that the percentage of the residue data lying below the LOQ is not large. The use of such methods can reduce the uncertainty in resulting estimations of human exposure. When using multiresidue scans to detect different compounds in one scan of one food sample, all results should be recorded together. This will make possible more accurate evaluation of exposure distributions for multiple chemicals. The committee does not recommend the routine application of adjustments for the percentage of the crop treated in estimating dietary exposure to pesticides. Adjustments for acreage treated are appropriate only under certain conditions. For example, such adjustments may be used when there is little regional variation in acreage treated, or when the crop is uniformly distributed at the national level. To determine total dietary exposure to a particular pesticide, intakes from all foods on which residues might be present need to be combined. Many pesticides are approved for use on more than one crop. In addition, a single crop may be used in the production of a variety of processed foods. To estimate the total dietary exposure to a particular pesticide, it is important to consider the contribution of all foods on which residues might occur. To properly evaluate the potential risk from exposure to multiple pesticides with common mechanisms of action, it is necessary to develop
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Pesticides in the Diets of Infants and Children measures of total exposure to pesticides within the same class that reflect the overall toxicity of all pesticides combined. Since the combined effect of pesticides acting by a common mechanism can be greater than the individual effect of any single pesticide, it is important to develop risk assessment methods that address the total risk from exposure to all pesticides within the same class. One possible approach is to establish toxicity equivalence factors based on no-observed-effect levels as was done for organophosphates in this chapter. Because infants and children are subject to nondietary sources of exposure to pesticides, it is important to consider total exposure to pesticides from all sources combined. REFERENCES Amdur, M.O., J. Doull, and C.D. Klaassen, eds. 1991. Caserett and Doull's Toxicology, 4th Ed. New York: Pergamon. 1033 pp. Ames, R.G., and J.W. Stratton. 1991. Acute health effects from community exposure to N-proply mercaptan from an ethoprop (Mocap R)-treated potato field in Siskiyou County, California. Arch. Environ. Health 46:213–217. Ames, R.G., S.K. Brown, J. Rosenberg, R.J. Jackson, J.W. Stratton, and S.G. Quenon. 1989. Health symptoms and occupational exposure to flea control products among California pet handlers. Am. Ind. Hyg. Assoc. J. 50:466–472. Arthur, R.D., J.D. Cain, and B.F. Barrentine. 1976. Atmospheric levels of pesticides in the Mississippi Delta. Bull. Environ. Contam. Toxicol. 15:129–134. Berteau, P.E., J.B. Knaak, D.C. Mengle, and J.B. Schreider. 1989. Insecticide absorption from indoor surfaces: Hazard assessment and regulatory requirements. Pp. 315–326 in Biological Monitoring for Pesticide Exposure: Measurement, Estimation and Risk Reduction, ACS Symposium Series 382, R.G.M. Wang, C.A. Franklin, R.C. Honeycutt, and J.C. Reinert, eds. Washington, D.C.: American Chemical Society. Buckley, J.D., L.L. Robison, R. Swotinsky, D.H. Garabrant, M. LeBeau, P. Manchester, M.E. Nesbit, L. Odom, J.M. Peters, W.G. Woods, and G.D. Hammond. 1989. Occupational exposures of parents of children with acute nonlymphocytic leukemia: A report from the children's cancer study group. Cancer Res. 49:4030–4037. Cade, P.H. 1989. Pesticide in lanolin [letter]. JAMA 262:613. CDHS (California Department of Health Services). 1980. Ventura County Environmental Health Department, Report to the California Department of Health Services. Sacramento, Calif.: California Department of Health Services. CDHS (California Department of Health Services). 1987. Report to the Legislature: Evaluation of Hazards Posed by the Use of Wood Preservatives on Playground Equipment . Department of Health Services, Office of Environmental Health Hazard Assessment. Berkeley, Calif.: California Department of Health Services. Cline, R.E., R.H. Hill, Jr. D.L. Phillips, and L.L. Needham. 1989. Pentachlorophenol measurements in body fluids of people in log homes and workplaces. Arch. Environ. Contam. Toxicol. 18:475–481. Dunphy, J., M. Kesselbrenner, A. Stevens, B. Vlec, and R.J. Jackson. 1980. Pesticide poisoning in an infant—California. MMWR 29:254–255. Ecobichon, D.J. 1991. Toxic effects of pesticides. Pp. 565–622 in Casarett and Doull's
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Representative terms from entire chapter: