DICAMBA RISK ASSESSMENT REPORT
DATE:
Author: Kimi Ceridon 61 Arlington Street Medford, MA 02155 857.523.0804 kceridon@kalepa-tech.com
7-December-2009
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ABSTRACT
Dicamba is a benzoic acid herbicide sold under many trade names and integrated into several pesticide products. There are several means of exposure to Dicamba including dietary exposure through food and water consumption, recreational exposure though interaction with treated lawns and turfs, residential exposure treatment of lawns and occupational exposure through treatment of crops and fields. The United States Environmental Protection Agency (US EPA) has established recommendations for the acute Average Daily Intakes that are above the values recommended by agencies with the World Health Organization (WHO) and the European Union (EU). It is recommended that the US EPA reevaluate this recommendation and adopt the WHO/EU values. This paper discusses supporting evidence and the reasons for this recommendation.
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INTRODUCTION
Dicamba is a benzoic acid herbicide sold under many trade names and integrated into several pesticide products. 1 It appears in both acid and salt forms with the following registered uses. On rights of way areas Asparagus Barley Field and pop corn Pasture and rangeland grasses Oats Proso millet Rye Sorgum Soybeans Sugarcane Wheat Notably, it has uses in both spot and broadcast lawn and golf course treatments and the rates of application vary from 0.5 to 2.8 pounds of acid equivalent per acre. Dicamba is also available in various products, formulations and 1 pesticide combinations. According to the United States Environmental Protection Agency (US EPA), “There were approximately 434 active products of Dicamba formulated from 6 different forms. The acid, dimethylamine and sodium salt ester forms of Dicamba have the most products. The products are formulated as liquids, standard granules and water dispersible granules. The residential products are typically formulated as granular weed and feed formulations or as liquids in concentrates or ready to use sprays.�
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(a)
(b) 2
Figure 2-1 – (a)Schematic Structure of Dicamba (b) 3-D rendering of Structure of Dicamba
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Dicamba is also known as 3,6-dichloro-o-anisic acid, 3,6-dichloro-2-methoxybenzoic acid or 2-methoxy-3,6dichlorobenzoic acid. It has a chemical formula of C8J6Cl2O3 with a molecular weight of 221.0. The molecular structure of Dicamba acid appears in Figure 2.1. Images of Dicamba salts do not appear in this summary. While US EPA recommends an acute Average Daily Intake (aADI) or Acute Reference Does (aRfD) of no more than 1 1.0 mg/kg-bw/day , the World Health Organization (WHO) and the European Union (EU) Commission Health and 4 Consumer Protection Directorate-General recommends an aADI or aRfD of no more than 0.3 mg/kg-bw/day . The following summary discusses risk assessments associated with Dicamba and evaluates the differences in the EPA and WHO/EU recommendations. Since Dicamba has several registered uses involving multiple routes and levels of exposure, the application rates range over five orders of magnitude. This assessment summarizes available information and verifies that the more stringent WHO and European Union standards can be met given the current application guidelines and available chemical evaluations. This is important in determining whether the US EPA standard can be adjusted to the WHO/EU standard without changing application and use recommendations. While it is not the intent of this report to recommend an unnecessarily conservative aADI, it is desired to reconcile these values and determine if the US EPA value is unnecessarily lenient given the current guidelines and uses for Dicamba. This assessment is largely based on evaluation of literature available to the public. No experimentation or testing was completed in relation to this characterization; it is quantified through calculations based on available data. From this evaluation, the risks associated with the identified hazards and exposures to Dicamba is discussed and summarized. While the exact reason for the differing recommendations is unclear, a difference in the calculations used to arrive at the recommendations is discussed. Finally, this assessment is summarized with a recommendation whether the aADI or aRfD recommended by the US EPC can be adjusted to the WHO/EU recommendation without modifying usage and application guidelines. From the available data and this assessment, it appears it is feasible to reduce the aADI from the current 1.0 mg/kg-bw/day to 0.3 mg/kg-bw/day with a few modifications in to use and application guidelines.. This assessment draws on information provided by A. Wallace Hayes of the Harvard School of Public Health as well as from other sources including a review of documents associated with the EPA Health Effects Division (HED) RePage 3
registration Eligibility Decision (RED) on Dicamba. The RED document was submitted in September 2005 with the final decision and final corrections completed in June 2009. Additional resources can be viewed in the RESOURCES section of this document.
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METHODS
Given the number of uses for Dicamba, a human can be exposed to it via a single exposure route or through a combination of exposure routes. Examples of potential exposure routes are ingestion of Dicamba residuals on food crops, ingestion of ground or surface water contaminated with Dicamba leached through soil, dermal exposure during lawn or golf course treatment and dermal exposure post treatment of a lawn or golf course. While this is a limited list of exposure routes, aggregating the identified hazards and exposures into a risk assessment is important to formulating means of mitigating the risks associated with Dicamba. The US EPA and the WHO/EU established various endpoints for exposure to Dicamba through animal studies. Notably “No Adverse Effect Limits” or NOAELs and “Lowest Adverse Effect Levels” or LOAELs were determined for various exposures. From examination of the literature, the animal studies were very similar if not the same. In the case for Acute Dietary exposure, the Acute Neurotoxicity Study resulted in an LOAEL and no LOAEL. The aADI or aRfD was established from the LOAEL using equation Eq 3-1: Eq. 3-1 In Eq 3-1, UF is the uncertainty factor used to account for interspecies extrapolation, interspecies variations and uncertainty in the observed values including converting from a LOAEL to a NOAEL. The Chronic Allowed Daily Exposure (cADI) or Chronic Reference Dose (cRfD) can be calculated as in Eq 3-1: Eq 3-2 In this case, the UFchronic is 100 where 10x accounts for interspecies extrapolation and 10x accounts for interspecies variation with no need for converting between LOAEL and NOAEL. While the US EPA uses aADI and aRfD, the RED reports findings in terms of the acute population adjusted dose (aPAD) or the chronic population adjusted dose (cPAD). These values incorporate an additional safety factor prescribed by the Food Quality Protection Act (FQPA) where aPADs are calculated according to equation Eq 3-3: Eq 3-3 The EPA reports the FQPA SF as 1X, so for the purposes of this report, aPAD is interchangeable with aRfD. In response to completing the Rerigistration Eligibility Decision (RED) Document for Dicamba, US EPA completed a modeling of dietary, residential, recreational, occupational and aggregate exposures scenarios using various exposure models. Since Dicamba is commonly used on right-of-way areas including golf courses and lawns, this assessment included examining exposures related to these locations. The modeling resulted aPADs and Margins of
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Figure 3-1 - Summary of Dietary Exposure for Dicamba – Food and Water
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Exposures (MOEs) for each scenario related to different portions of the population. A example of one of the resulting series is shown in figure 3-1. The MOEs is a predetermined value based on the level of concern for exposure. This value is compared to the ratio of NOAEL to the Estimated Exposure dose and should meet the criteria shown in equation Eq 3-4 for the risk of exposure to be deemed below the level of concern. Eq 3-4 Since the NOAEL is the same for both the USEPA and the WHO/EU studies, the calculations of MOE are equivalent and documentation for MOEs established by the WHO or EU were not found. The MOEs targeted by the EPA for Dicamba are shown in figure 3-2.
Figure 3-2 - Summary of Target Margins of Exposure (MOEs) for Risk Assessment1
It is noted that MOE is approximately the inverse of the Hazard Quotient which is defined as shown in equation Eq 3-5 Eq 3-5
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If HQ were the exact inverse of MOE, figure 3-2 would reflect only values of 1 where target ratios would be greater than unity. HQ differs from MOE in that acceptable values are less than 1 and aADI or aRfC is used in place of NOAEL. Given this substitution, conclusions based on HQ may differ than those based on MOE. An example of MOEs presented by the EPA can be seen in Figure 3-3 Since the US EPA has made available extensive exposure modeling results, it is also deemed unnecessary to reevaluate the estimated exposure except as means of evaluating the order of magnitude of the values presented for validity. For this exercise, equation Eq 3-6 is used to calculate the Average Daily Dose. Eq 3-6 Where C is the mean exposure concentration, IR is the injestion rate, B is the bioavailability, BW is body and AT is the averaging time. For Dicamba, the US EPA reports a maximum residual food concentration of 6 ppm for Barley. Given the quantity and quality of the information available, it is reasonable to evaluate whether the US EPA recommended ADI can be adjusted to the more conservative value recommended by the WHO/EU.
Figure 3-3 Dicamba Short Term MOEs for Homeowner Applications to Lawns (Application Rate = 1.0 lb ai/acre)
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RESULTS
For Eq 3-1, both the US EPA and the WHO/EU report a LOAEL of 300 mg/kg-bw/day. The primary difference between the calculations by the US EPA and the WHO/EU is in the Uncertainty Factors. The US EPA uses a UF acute of 300 for the calculation of aRfD where 10x accounts for interspecies extrapolation, 10x accounts for interspecies variation and 3x accounts for converting from LOAEL to NOAEL. A 3x is used because, according to the US EPA, “A comparison with rat development toxicity study that had similar clinical signs” . . . “indicates that the NOAEL for the acute neurotoxicity is unlikely to be more than 3-fold lower than the LOAEL.” On the other hand, the WHO/EU study indicates a UFacute of 1000 where the 3x is replaced by 10x. Using these values, it can be seen that the ADI established by the US EPA is 1.0 mg/kg-bw.day while the WHO/EU establish a value of 0.3 mg/kg-bw/day. It is also be noted the US EPA reports a NOAEL for chronic dietary exposure of 45mg/kg-bw/day. With a UF of 100x, the result is a cADI or cRfD of 0.45 mg/kg-bw/day. This value is below that of the aADI or aRfD.
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While the US EPA used sophisticated models such as DEEM-FCID to establish acute dietary exposures the ADD was approximated using Eq 3-6 to approximate an ADD. This exercise was done simply to validate the order of magnitude of values reported by the US EPA. Assuming the a 70kg person eats 4-5 pounds (1.8-2.3 kg) of food per day using an approximate conversion of 1 kg/L with a 6ppm concentration aggregated over the entire daily dietary intake and a bioavailability of 100% to be conservative, the calculated ADD is as follows.
These values are larger than those reported in figure 3-1 due to the conservative estimates used. Notable, it is not likely that 100% of daily food intake will contain the maximum residual of 6 ppm of Dicamba. Judging from this conservative calculation, the values reported in figure 3-1 are considered valid and no further exploration of ADD is completed. Reviewing the values of aPAD reported by the EPA and re-evaluating them for HQ for the values reported in figure 3-1, the new values using both the US EPA recommendation and the WHO/EU recommendation is shown in figure 4-1 result. If this exercise is repeated for all dietary exposures presented by the US EPA, the outcome is uniformly values less than unity. Acute HQ HQ Dietary Exposure US EPA WHO/ EU mg/kg-bw/day Population Sub Group aADI = 1.0 mg/kg-bw/day aADI = 0.3 mg/kg-bw/day General Population 0.0435 0.0435 0.1450 All Infants (<1 year old) 0.108 0.1080 0.3600 Children 1-2 years old 0.0756 0.0756 0.2520 Children 3-5 years old 0.0675 0.0675 0.2250 Children 6-12 years old 0.0476 0.0476 0.1587 Youth 13-19 years old 0.0318 0.0318 0.1060 Adults 20-49 years old 0.0341 0.0341 0.1137 Adults 50+ 0.0267 0.0267 0.0890 Females 13-49 years old 0.0312 0.0312 0.1040 Figure 4-1- Summary of Dietary Exposure for Dicamba â&#x20AC;&#x201C; Food and Water for recommended aADI
Similarly, examining the MOEs reported by the US-EPA as shown in Figure 3-4, the MOEs can be recalculated as HQs. The resulting values are shown in Figure 4-2.
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mg/kg/day
HQ US EPA aADI = 1.0 mg/kg-bw/day
HQ WHO/ EU aADI = 0.3 mg/kg-bw/day
0.023
0.0058
0.0058
0.0193
0.023
0.0054
0.0054
0.0180
3. Load/Apply Granules with a Broadcast Spreader
0.5
0.00073
0.0007
0.0024
4. Mix/Load/Apply with a Hose-end Sprayer (Mix your own)
0.5
0.012
0.0120
0.0400
5. Mix/Load/Apply with a Hose-end Sprayer (Ready to Use)
0.5
0.0029
0.0029
0.0097
6. Mix/Load/Apply with Hand Held Pump Sprayer
0.023
0.0019
0.0019
0.0063
7. Mix/Load/Apply with Ready to Use Sprayer
0.023
0.0027
0.0027
0.0090
Treated Area
Combined Dose
acres/day
1 Hand Application of Granules 2 Belly Grinder Application
Scenario
Figure 4-2 - Dicamba Short Term HQs for Homeowner Applications to Lawns (Application Rate = 1.0 lb ai / acre
Again, the results are reflective of the findings by the US EPA. In cases where the US EPA calculated exposures well below the level of concern where the MOE is much greater than the established values, the corresponding HQ in much less than unity. All of the calculations for MOE presented by the US EPA are not repeated here, but where the US EPA did report exposure levels above the level of concern, the calculated HQ provides similar results. With regards to occupational exposures, US EPA modeling did find several scenarios where the baseline exposure is above a level of concern based on established MOEs that are typically 100. In this case, the baseline scenario is for occupational applications of Dicamba where no protective equipment is employed. When protective equipment is used, the MOEs indicate the level of concern is diminished with margins approaching those of recreational exposures. The calculations of HQ for both the recommended US EPA aADI and WHO/EU aADI did not result in any crossover of these marginal points.
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DISCUSSION
Given the quantity and quality of data available on Dicamba, it is reasonable to assume that the risks associated with exposure to the chemical are well established for the current recommended uses. From the available information, the established means of exposure to Dicamba commonly fall below levels of concern established by the US EPA through the current recommended aADI reported as MOE and aPAD values. Additionally, they are also below levels of concern when the means are exposure are reevaluated using aADI values recommended by the WHO/EU. These results indicate that there is no apparent reason why the US EPA cannot adopt the more stringent aADI values recommended by the WHO/EU. In the case of acute dietary exposure, HQs were calculated using both the current US EPA aADI value and the WHO/EU aADI value. The modeling shows the exposure is substantially below levels of concern resulting in low percentage aPADs and HQs much less than unity. Although the calculations are not presented in this paper, this is also true when accounting for recreational exposures due to Dicamba use on right-of-way, turfs, golf courses and lawn. As reported by the US EPA, exposure during application without the use of recommended protective equipment results in HQs greater than unity, aPADs above 100% and MOEs below the recommended 100. In these scenarios,
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as the US EPA has already established, protective equipment should be warn for occupational applications. This recommendation does not change in light of the WHO/EU aADI values. Although this paper focused primarily on the acute ADI value, it is also interesting to note that the chronic ADI value is less than half of the acute ADI value. For this reason, it is not apparent why a higher valued aADI is used at all for establishing guidelines. At the very least, the more conservative cADI value of 0.45 mg/kg/day should be used to establish application and usage guidelines. Given the wide margins of safety for the known current exposures to Dicamba, there is no reason to not adapt the WHO/EU standard. There are three motives for this recommendation. First, since the WHO/EU values do not drastically change the current exposure scenarios or diminish the application guidelines, there is no commercial, industrial, economic or political reason the new aADI cannot be met at this time. Second, had the margins been smaller, arbitrarily adapting the WHO/EU values can result in unintended consequences where the use of Dicama is displaced with either a less commercially attractive or more toxic alternative. Third, since the margins are relatively large regardless of whether the current US EPA aADI or the WHO/EU aADI is used, there is no reason to allow such margins and potentially encouraging expanded use of Dicamba thereby increasing exposure. Even with the newly adapted aADI, there is room for expanded use without approaching levels of concern.
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REFERENCES 1.
2. 3. 4.
Olinger, C and Yung, Y, 13-September-2005, Memorandum : HED Chapter of the Reregistration Eligibility Decision Document (RED) â&#x20AC;&#x201C; Phase I PC Code 029801; DP Barcode D317720, United States Environmental Protection Agency, Washington, DC Image from Dicamba on Wikipedia.org posted via Merck Index, 11th Edition, 3026 Image from National Pesticide Information Center, Dicamba (General Fact Sheet), reviewed January 2002 Final: Review report for the active substance Dicamba, Finalized in the Standing Committee on the Food Chain and Animal Health at its meeting on 14 March 2008 in view of the inclusion of Dicamba in Annex I of Directive 91/41/EEC, European Commission Health & consumer Protection Directorate-General.
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