Food Safety Special Issue: Pesticide food safety standards as companions

Transcription

1 1 2 3 Food Safety Special Issue: Pesticide food safety standards as companions to tolerances and Maximum Residue Limits 1 4 Carl K. Winter, Elizabeth A. Jara, 5 Department of Food Science and Technology, University of California, Davis, CA, USA 6 Abstract Allowable levels for pesticide residues in foods, known as tolerances in the US and as Maximum Residue Limits (MRLs) in much of the world, are widely yet inappropriately perceived as levels of safety concern. A novel approach to develop scientifically defensible levels of safety concern is presented and an example to determine acute and chronic Pesticide Food Safety Standard (PFSS) levels for the fungicide captan on strawberries is provided. Using this approach, the chronic PFSS level for captan on strawberries was determined to be 2000 mg kg -1 and the acute PFSS level was determined to be 250 mg kg -1. Both levels are far above the existing tolerance and MRL levels that commonly range from 3 to 20 mg kg -1, and provide evidence that captan residues detected at levels greater than the tolerance or MRLs are not of acute or chronic health concern even though they represent violative residues. The benefits of developing the PFSS approach to serve as a companion to existing tolerances/mrls include a greater understanding concerning the health significance, if any, from exposure to violative pesticide residues. In addition, the PFSS approach can be universally applied to all potential pesticide residues on all food commodities, can be modified 1 Correspondence: Carl K. Winter, ckwinter@ucdavis.edu

2 by specific jurisdictions to take into account differences in food consumption practices, and can help prioritize food residue monitoring by identifying the pesticide/commodity combinations of greatest potential food safety concern and guiding development of field level analytical methods to detect pesticide residues on prioritized pesticide/commodity combinations Keywords: pesticide residues, food safety, tolerances, Maximum Residue Levels, MRLs, regulation, reference dose, captan, strawberries 28

3 Background The topic of pesticide residues in foods represents a controversial and complicated issue of interest to consumers, food producers and processors, regulators, legislators, and scientists throughout the world. Consumer concern regarding pesticide residues has led, in part, to the steady growth of the organic food industry, for which global international sales were estimated to be more than $63 million USD in 2011 (IFOAM 2014), and for which US retail sales were estimated to be more than $35 million USD in 2013 (OTA 2014). Regulatory scrutiny has also been called into question for perceived deficiencies in food sampling and analytical methods used; a recent report from the US Government Accountability Office criticized residue monitoring approaches used by the US Food and Drug Administration (FDA) and the US Department of Agriculture (USDA) (GAO 2014). A previous study by the US General Accounting Office indicated that foods containing violative pesticide residues, particularly those imported from other countries, frequently reached consumers (GAO 1992) Concerns regarding pesticide residues in foods remain present even though risk assessment studies have continuously concluded that consumers are exposed to only small amounts of pesticide residues in their foods (Winter 1992). Consumer exposure to residues of common pesticides on foods alleged to represent those most contaminated by pesticide residues frequently is at least one million times lower than the No Observed Adverse Effect Levels determined from long term animal feeding studies (Winter and Katz 2011) It appears as though much of the consumer and regulatory concern regarding pesticide residues in foods may result from findings demonstrating that pesticide residue violations occur at rates often ranging from one to five percent, depending upon the food commodity

4 analyzed and the geographical origin of the food (FDA 2014). If such rates are representative of the overall food supply, it is clear that consumers are frequently exposed to violative residues of pesticides in their foods It is challenging to reconcile the apparently contradictory findings that consumers are typically exposed to small levels of pesticide residues but that consumers frequently consume food containing violative pesticide residues. This challenge is reflective of the counterintuitive nature by which allowable levels of pesticide residues are established. In short, allowable pesticide residue levels, known as tolerances in the US and as Maximum Residue Limits (MRLs) in most of the rest of the world and expressed in terms of mg of pesticide/kg food are not established as safety standards, and violative residues are rarely of health significance In this review, the relationship (or lack thereof) between tolerances/mrls and safety is examined. A companion approach to establish scientifically defensible food safety standards for specific pesticide/commodity combinations is proposed. Simple examples of the development of such safety standards using monitoring data and common risk assessment methods are provided, and the benefits of using this approach as a companion to tolerances/mrls are discussed Analysis Establishment of pesticide tolerances and MRLs Methods used to establish pesticide tolerances and MRLs are confusing and complicated among scientists, regulators, legislators, and consumers. Intuitively, one would expect tolerances/mrls to reflect safe levels of exposure and strong arguments can be made that established tolerances/mrls are protective of public health. It is also intuitive to assume that

5 pesticide residues detected in violation of legal limits would represent unsafe levels of pesticide residues. This assumption, however, is nearly always incorrect. To understand why consumption of foods containing violative residues of pesticides is rarely of human health concern, it is important to understand the process by which tolerances and MRLs are established. This topic was the subject of a lengthy review article and is summarized and updated below (Winter 1992; EPA 2012) In the US, pesticide tolerances are approved by the US Environmental Protection Agency (EPA) provided that the intended uses of the pesticide pose a reasonable certainty of no harm to consumers following consideration of pesticide residue data, food consumption data, and toxicology information. In accord with the Food Quality Protection Act of 1996 (US Congress 1996), the reasonable certainty of no harm criterion requires consideration of the potential risks to sensitive population subgroups such as infants and children. In addition, the law requires consideration of aggregate exposure to the pesticide from food, drinking water, and other residential sources. The cumulative effects from all members of a pesticide family that possess a common toxicological mechanism of action must also be considered If the intended use of a pesticide on specific crops has the potential to result in a food residue, the manufacturer of the pesticide is required by the EPA to perform a series of field studies to document the incidence and levels of pesticide residues on those crops prior to being granted an approval to use the pesticide on the crops. Such field studies are typically performed under Good Agricultural Practice (GAP) conditions specified on the product label that would be expected to yield the highest residue levels; such worst-case conditions include applying the pesticide at the highest recommended rate of application to control the desired pest, applying the pesticide the maximum number of times anticipated during the growing season,

6 and allowing for the shortest anticipated interval between the final pesticide application and harvest The EPA makes use of the residue data generated by the pesticide manufacturer to assess the distribution of residues and combines this information with food consumption data to estimate potential consumer exposure to the pesticide from all commodities for which it is registered as well as for any proposed new uses. Consumer exposure to the pesticide is compared with toxicological criteria such as the acute and chronic reference dose (RfD) or Acceptable Daily Intake (ADI), which are expressed in terms of mg of pesticide/kg of body weight per day, and the cancer potency factor (Q*). The pesticide presents a reasonable certainty of no harm in the event that chronic exposure from the pesticide to the general population and to sensitive population subgroups is below the chronic RfD, that acute exposure for sensitive population subgroups has at least a 99.9 percent probability of being below the acute RfD, and that potential cancer risks are below an estimated incidence of one excess cancer per million based upon methods likely to exaggerate the actual cancer risks (Winter and Francis 1997; EPA 2014) If it is concluded that all current and proposed uses of the pesticide present a reasonable certainty of no harm to consumers and that the benefits from the use of the pesticide outweigh any other risks such as environmental impacts or worker safety concerns, the pesticide will be registered for use on the new proposed commodities and tolerances will be established on new commodities for which the pesticide might leave residues. If a reasonable certainty of no harm is not concluded, the pesticide will not be registered for its proposed use and no tolerance will be established.

7 An understanding of the process used to establish the actual tolerance level is critical to enable proper interpretation of the utility of tolerances and their lack of relevance as safety standards If the pesticide is approved for use on a proposed commodity, the actual tolerance level is derived from consideration of the results from the worst-case field studies from the most critical GAP described above. Typically, the manufacturer will petition the EPA to establish a tolerance at or slightly above the highest level observed from all of the field studies. The selected tolerance level is frequently much higher than the normal levels of residue detected and can be considered to represent the maximum residue level expected from the legal application of the pesticide As a result, pesticide tolerances are best considered as food quality standards rather than as food safety standards, and represent an enforcement tool designed to ensure that pesticide applications are made in accordance to regulations. Residues detected in excess of established tolerances indicate likely pesticide misuse since legal applications would generally result in residues at or, more commonly, well below the established tolerance Pesticide residue violations in the US also result when a pesticide is detected on a commodity for which no tolerance has been established. This is the most frequent type of residue violation in the US. In 2011, FDA pesticide residue monitoring indicated that 16 of the 17 pesticide residue violations for domestic foods and 331 of 346 pesticide residue violations for imported foods were in this category (FDA 2014) Many countries throughout the world rely on MRLs established by the United Nations Food and Agriculture Organization and the World Health Organization (FAO/WHO) Codex Committee on Pesticide Residues. The approaches used in setting MRLs are similar to those used by the US for establishing tolerances; agricultural practices and field residue studies are

8 considered to determine MRLs provided that risk assessment indicates that foods containing the pesticide residues are safe to consume. Although there is considerable effort devoted to harmonizing tolerances and MRLs, there are many pesticide/commodity combinations for which the tolerances and MRLs differ. Such differences may arise from different GAPs used in different regions, differential treatment of pesticide metabolites and environmental breakdown products, and differences in crop groupings and crop names. More detailed information about the practices used to set Codex MRLs and to assess dietary intake to pesticides is available in a training manual developed for members of the FAO/WHO Joint Meeting on Pesticide Residues (FAO 2011) The determination by the EPA that the typical use of a pesticide on all registered commodities represents a reasonable certainty of no harm for consumers indicates that the anticipated exposure to the pesticide, even for sensitive population subgroups, is at levels below those triggering health concerns such as the acute or chronic RfD or the ADI. In many cases, this determination may also indicate that typical consumer exposure to residues of several pesticides is far below levels of health concern and that much greater levels of exposure might still result in a reasonable certainty of no harm. Thus, tolerances and MRLs are capped at the highest residue levels anticipated from the legal use of pesticides even though much higher levels might be acceptable from a health standpoint. It follows that violative residues, occurring when residues exceed tolerances or MRLs or when residues are encountered that do not have tolerances established, are rarely of health concern (Winter 1992; Katz and Winter 2009) Establishing pesticide food safety standards To illustrate the potential differences between pesticide tolerances/mrls and levels of health concern from pesticide residues, it is proposed for the first time that Pesticide Food Safety

9 Standard (PFSS) levels be established as companions to tolerances/mrls. A PFSS level can be established for any specific pesticide/commodity combination and can be useful in the assessment of the health significance of a violative pesticide residue From a toxicological perspective, violative residues would be considered to pose safety risks only when consumption of the violative residue would result in a single day s exposure exceeding the acute RfD or when continuous exposure to the violative residue for extended periods of time would cause the chronic RfD to be exceeded The development of scientifically defensible methods to calculate PFSS levels is challenging. Many pesticides are used on several different foods, so it is important to consider exposure to the pesticide from all foods and not just on the commodity for which the PFSS level is determined. A simple example for developing PFSS levels for the fungicide captan on strawberries is presented below; strategies to consider the impact of single pesticide use on multiple foods are provided in the Recommendations and Conclusion section Captan in strawberries Captan (N-(trichloromethylthio)cyclohex-4-ene-1,2-dicarboximide) is a broad spectrum fungicide used to control a variety of fungal diseases on many common fruits and vegetables (Tomlin 1994). It is frequently used on strawberries and was the subject of a controversial 1994 television program in which the differences between allowable levels of captan on strawberries in the US (25 mg kg -1 ) and in Canada (5 mg kg -1 ) were identified and characterized by one guest on the program to represent inadequate regulation on the part of the EPA (Winter 1994). The tolerances and MRLs for captan on strawberries continue to vary in different geographical regions of the world; the current US tolerance is 20 mg kg -1 while MRLs are 15 mg kg -1 (Codex), 3 mg kg -1 in the European Union, 10 mg kg -1 in Australia, 5 mg kg -1 in Korea, 15 mg kg -1 in China, and 20 mg kg -1 in Japan (Global MRL Database 2015).

10 In 2012, the California Department of Pesticide Regulation (CDPR) analyzed 170 strawberry samples grown in California, other locations in the US, and from other countries for captan residues (CDPR 2013). Captan was positively detected in 107 (63 percent) of the samples. Captan residues were much less frequently detected on all of the other fruits and vegetables analyzed (more than 160 different commodities were sampled) Chronic dietary exposure of the general US population to captan was estimated using Lifeline 5.0 software (The Lifeline Group, Inc, Annandale, VA, USA). The Lifeline model considers both food consumption and residue data to estimate exposure. Residue data from the 2012 CDPR database was entered for all commodities from which positive captan residues were detected. Analysis considered all specific residue findings rather than mean or median levels; all findings below the limit of detection were considered to contain no residue. A population size of 500 was used and considered daily exposures for each member of the population from birth until 70 years of age The average daily dietary exposure to captan from fruits and vegetables was estimated to be 0.09 g/kg/ bw/day. Strawberries, by far, represented the greatest contributor to overall captan exposure at 0.08 g/kg bw/day. The chronic RfD for captan, according to the EPA, is 130 g/kg bw/day (IRIS 2014). Exposure to captan from all fruits and vegetables represented 0.07 percent of the RfD while exposure from strawberries represented 0.06 percent of the RfD This example illustrates that captan exposure from consumption of fruits and vegetables represents only a tiny fraction of the RfD and that most of the exposure to captan comes from consumption of strawberries.

11 A chronic PFSS level for captan on strawberries was developed using Lifeline 5.0 software by varying concentrations of captan residues on strawberries until the estimated exposure approximated the chronic RfD. Exposure to captan from all other commodities was considered to be negligible based upon exposure estimates presented previously. Using this approach, a chronic PFSS level for captan on strawberries was determined to be 2000 mg kg -1. To place this value in perspective, average consumers of strawberries would have to be exposed to 2000 mg kg -1 of captan on all strawberries they consume throughout their lifetimes for their exposure to reach the chronic RfD, a condition that is not remotely possible based upon current captan use and residue patterns. Thus, it can be concluded that exposure to violative captan residues on strawberries is not of chronic health concern An acute PFSS level for captan on strawberries can be calculated by determining residue levels that could lead to exposures for high frequency strawberry consumers at the acute RfD. As an example, data from the US National Health and Nutrition Examination Survey identified 2-5 year-olds as the population subgroup most likely to consume berries (NHANES 2013). This database did not differentiate the various types of berries, so it is conservatively assumed in this example that all berries consumed were strawberries. Further analysis of the berry consumption database allowed determination of an upper 95 th percentile of berry consumption for 2-5 year-olds. Using this upper percentile for berry consumption and considering EPA s acute captan RfD of 300 g/kg/day (IRIS 2014), an acute PFSS level of 250 mg kg -1 was determined, representing the concentration of captan residues on strawberries necessary for upper percentile 2-5 year-old berry consumers to reach the acute RfD A review of CDPR pesticide residue monitoring results from indicates that the maximum residue of captan detected on strawberries was 20 mg kg -1 (CDPR 2013). The

12 maximum residue exceeded 15 mg kg -1 (a violation in the EU, Korea, Australia, and China) in four of the ten years, and the maximum residue exceeded 10 mg kg -1 (a violation in the EU and Korea) in seven of the ten years The US tolerance, MRLs for various countries, maximum residue detected, and acute PFSS level for captan on strawberries are compared in Figure 1. It is clear from this figure that the acute PFSS level is far greater than the US tolerance, the various MRLs, and the maximum residue detected. Such findings reinforce the notion that violative residues of captan on strawberries are not indicative of unsafe levels of residues, even though a small number of residues identified from the CDPR monitoring programs would have been considered violative had they been detected in sampling programs conducted by the EU, Korea, Australia, or China Fig. 1 Comparison of the US tolerance, MRLs from various countries, and maximum residue detected for captan on strawberries with the acute Pesticide Food Safety Standard (PFSS) level. All values listed as mg pesticide/kg food.

13 Recommendations and conclusion This manuscript expands on the notion that violative pesticide residues are rarely of human health significance and provides an example of methods that can be used to develop PFSS levels as more appropriate levels of safety concern The example of captan residues on strawberries is one of many in which allowable levels of residues of a specific pesticide on a specific commodity may vary dramatically between different jurisdictions. Such differences in allowable levels are commonly interpreted to imply that jurisdictions allowing higher levels of residues may be inappropriately regulating the pesticides and potentially endangering public health. By understanding how such different regulatory limits compare with PFSS levels, it is possible to ascertain the degree, if any, by which the differing standards could compromise public health. In the case of captan on strawberries, for example, levels of safety concern are significantly higher than those of any of the allowable levels, rendering the differences in allowable levels moot with respect to health concerns. In terms of international trade, however, such differences in allowable levels could significantly impact agricultural production practices as well as serving as potential non-tariff trade barriers among nations engaged in commerce. It is hoped that an approach such as the development of PFSS levels could be useful in facilitating broader harmonization of tolerances/mrls throughout the world by illustrating that present differences in tolerance/mrl levels may not be of health significance The captan on strawberries example is a fairly simple one involving a pesticide for which typical dietary exposure is far below levels of health concern and for which the majority of exposure to the pesticide was from a single commodity. Development of PFSS levels for other pesticides on other crops may be more complicated in the event that background dietary

14 exposure to a specific pesticide may reflect significant contributions from a variety of food items; in such a case, methods to develop PFSS levels for specific pesticide/commodity combinations must consider the potential for exposures to the pesticide on other commodities and take such exposures into consideration. In addition, the development of PFSS levels for pesticides representing members of pesticide families possessing common mechanisms of toxic action, such as the organophosphate and carbamate insecticides, will require a solid understanding of the background levels of exposure to all pesticide family members on all commodities While it is clear that tolerances/mrls for pesticides are not appropriate to serve as safety standards, they play an important role as enforcement tools to determine, following pesticide residue monitoring, if pesticide applications have been made according to directions and their existence provides an economic deterrent for not following pesticide application directions. As such, it is envisioned that PFSS levels serve as companions, rather than replacements, for existing tolerances/mrls The development of methods to calculate PFSS levels for specific pesticide/commodity combinations has significant benefits to the international agricultural and regulatory communities: Education regarding the health significance of violative residues and the proper interpretation of tolerances/mrls. Public concern is frequently raised concerning the safety of the food supply when the detection of violative pesticide residues is publicized or in cases where different jurisdictions apply different residue standards. By comparing PFSS levels with the levels identified from violative samples, it is possible to determine the health significance, if any, of violative residues.

15 Universal nature of PFSS levels. Provided that data exist for pesticide toxicity and food consumption patterns, it is possible to develop PFSS levels for all potential combinations of pesticides and food commodities. Such an approach can be useful in the event that residues are detected on a commodity for which no tolerance/mrl has been established; a comparison of the levels detected with the PFSS level can immediately indicate the potential for harm that the residues possess Portability of PFSS levels. PFSS levels may differ in different regions of the country since food consumption patterns are not uniform throughout the world. PFSS levels can be calculated in any region of the world where adequate food consumption data exist Prioritizing pesticide residue monitoring programs. If it is desired to develop pesticide residue monitoring programs focusing on food safety rather than on tolerance/mrl enforcement, PFSS levels could be used to guide monitoring efforts by placing greater emphasis on monitoring pesticide/commodity combinations for which the differences between PFSS levels and potential realistic residue levels are the smallest and for which pesticide residues may be frequently detected Developing rapid field-level tests for residues of priority pesticide/commodity combinations. It is likely that most PFSS levels will be much higher than existing tolerance/mrl levels. As such, monitoring of pesticide residues at the PFSS level may not require the analytical sophistication of methods that enforce tolerance/mrl levels. Specific field-level tests with lower sensitivity such as colorimetric methods or Enzyme-Linked Immunosorbent Assay (ELISA) techniques might be developed that could be performed quickly and inexpensively at the site of pesticide application prior to harvest to ensure that PFSS levels are not exceeded. 324 References

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