Finally, Table V 4 summarizes the EECs for ETU, in ppb, which were obtained for the highest peak values ( Peak) along with those after 96 hours; 21/ 60 and 90 days; the yearly average and the average for all years. These EEC values were used in the ecological risk assessment for aquatic systems. 18 USEPA/ Office of Water 1993. Federal State Toxicology and Risk Analysis Committee ( FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines.

35 Table V 4. PRZM/ EXAMS farm pond modeling results for ETU ( EECs for ETU in ppb).

Scenario Peak 96 hr 21 Day 60 Day 90 Day Yearly Average Average of All Years FL peppers 12.3 10.0 6.5 3.2 2.2 0.6 0.3 FL turf 1 11.5 9.5 5.4 2.9 2.0 0.5 0.4 NC apples 11.2 9.7 7.4 4.1 2.8 0.7 0.6 FL sweet corn 11.0 9.0 5.2 3.1 2.1 0.6 0.4 FL tomatoes 10.9 8.6 4.3 2.7 1.9 0.5 0.4 CAalmonds 10.2 8.8 7.0 4.1 2.8 0.7 0.6 PA tomatoes 9.4 7.8 5.1 3.4 2.5 0.7 0.5 PAapples 8.7 7.5 6.0 3.4 2.3 0.6 0.5 CA onions 8.6 7.0 5.6 4.9 3.7 0.9 0.9 OR apples 7.6 6.6 5.4 3.2 2.2 0.6 0.5 NC peanuts 6.2 5.3 3.8 2.2 1.5 0.4 0.3 CA grapes 5.2 4.5 3.9 2.8 2.0 0.5 0.5 FL cabbage; Jan application 4.8 4.2 2.9 1.9 1.3 0.3 0.2 ME potatoes 4.3 3.7 2.9 2.1 1.6 0.5 0.4 MN sugar beet 4.3 3.6 2.4 1.7 1.3 0.4 0.3 FL cabbage; Oct application 3.9 3.0 2.0 1.3 0.9 0.2 0.2 TX wheat 3.9 3.1 1.9 0.8 0.6 0.1 0.1 CA sugar beet 3.2 2.9 2.5 1.8 1.3 0.3 0.3 IDpotatoes 2.8 2.3 2.0 1.6 1.1 0.3 0.3 CA tomatoes 2.6 2.0 1.6 1.3 0.9 0.2 0.2 OR sweet corn 2.5 2.1 1.5 0.7 0.6 0.2 0.1 OR wheat 2.2 1.9 1.4 0.8 0.5 0.1 0.1 ND wheat 2.2 1.8 1.3 0.6 0.4 0.1 0.1 1 These are the results for one application ( 17.4 lbs a. i/ acre). The results for three applications ( 17.4 lbs a. i/ acre each) are as follows ( ETU in ppb):

For 5 day intervals: 26.7 ( Peak); 22.4 ( 96 hr); 16.5 ( 21 Day); 8.6 ( 60 Day); 5.8 ( 90 Day); 1.5 ( Yearly); and 1.0 ( All Years); and For 7 day intervals: 32.0 ( Peak); 26.4 ( 96 hr); 16.5 ( 21 Day); 8.5 ( 60 Day); 5.8 ( 90 Day); 1.4 ( Yearly); and 1.0 ( All Years).

b. Drinking Water Assessment Ethylenethiourea ( ETU) is a common metabolite of all of the EBDC fungicides and may reach both surface and groundwater under some conditions. In contrast, parent EBDCs metiram, maneb and mancozeb are short lived in soil and in water and would not themselves be expected to remain in surface water long enough to reach a location that would supply water for human consumption whether from surface or ground water. ETU is not regulated under the Safe Drinking Water Act with no established MCL. However, since ETU is a B2 carcinogen, drinking water health advisories have been set by the EPAs Office of Water. Concentration values were set at 15 µ g/ l ( ppb) in Florida and 3 µ g/ l ( ppb) in Maine18.

EDWCs of ETU is included in detail in Appendix VI ( Memorandum to HED dated 08/ 25/ 04). In this memorandum, these values were calculated for use in an FQPA human health risk assessment. This is a revised memo presenting the Estimated Drinking Water Concentrations ( EDWCs) for the EBDC degradate ETU for use in an FQPA human health risk assessment. The referenced assessment addresses exposure to ETU only. The chronic EDWC for surface water is 0.1 ppb and is based on a monitoring study conducted by the EBDC Task Force. A range of acute EDWCs is established with 36 a lower limit of 0.1 ppb ( based on monitoring) and an upper limit of 25.2 ppb ( based on environmental fate and transport simulation modeling using the linked EPA PRZM and EXAMS models). The ground water EDWC is 0.21 ppb ( based on a targeted monitoring study).

As suggested by the registrant, EFED used NASS reported typical highest one in ten years application rate of 1.18 lb a. i./ A ( 0.11 kg/ hac ETU) in conducting a new PRZM/ EXAMS run for the upper acute limit of 25.2 ppb ( FL peppers). The rate was inferred from NASS summaries ( refer to the table provided by the registrant below). As expected the upper acute limit of 25.2 ppb ( FL peppers) has changed to 10.7 ppb; this value was reported in a new memo for HED.

Table: NASS maneb pepper actual use information as reported by the registrant from: www. pestmanagement. inf/ nass Active Ingredient Per Application ( lb/ appli./ ac)

Year Minimum Maximum Average 1992 1.19 1.37 1.26 1994 0.98 1.27 1.13 1996 1.09 1.31 1.19 1998 1.03 1.14 1.08 2000 0.97 1.65 1.21 2002 1.01 1.45 1.23 Note: the average of the six yearly averages is 1.18 lb a. i./ A, equivalent to an ETU rate of 0.11 kg/ ha. 37 VI. Aquatic Exposure and Risk Assessment a. Hazard Summary ( Acute/ Chronic)

Based on acute exposure from core studies, ETU is practically nontoxic to cold water fish ( rainbow trout LC 50 > 502 ppm based on measured samples) and slightly toxic to freshwater invertebrates ( daphnid EC 50 = 26.9 ppm based on measured samples). These two studies fulfill guidelines 72 1( c) for freshwater fish and 72 2( a) for freshwater invertebrates. A Tier II ( guideline 123 2) supplemental study for Pseudokirchneriella subcapitata ( formerly Selenastrum capricornutum), a freshwater green alga, showed an ETU EC 50 of 23.0 ppm a. i. based on a decline in cell density. EFED classified this study as supplemental because the test duration was only 72 hours and the guidelines require the test duration to be 120 hours.

EFED has limited acute toxicity data to evaluate ETU's toxicity to aquatic organisms. EFED is requiring submission of or reserving submission for the following guidelines studies:

72 1( a) Acute Fish Toxicity Bluegill a freshwater fish dwelling in warm waters 72 3( a) Acute Estuarine/ Marine Toxicity Fish 72 3( b) Acute Estuarine/ Marine Toxicity Mollusk 72 3( c) Acute Estuarine/ Marine Toxicity Shrimp 72 4( a) Early Life Stage Fish for freshwater and estuarine/ marine species 72 4( b) Life Cycle Aquatic Invertebrate for freshwater and estuarine/ marine species 122 2 ( Tier I) or 123 2 ( Tier II) Aquatic Plant Growth EFED needs submission of these studies for the TGAI of ETU. The first study listed above [ 72 1( a)] is a basic study need for all pesticides. EFED is requiring this study for ETU because ETU is a degradate toxic to mammals which may also be toxic to aquatic wildlife. The next three studies [ 72 3( a, b, and c)], deal with the acute toxicity to estuarine and marine species. EFED needs these studies because of the EBDCs' use in coastal counties where EFED expects estuarine or marine exposure to the EBDCs and their common degradate, ETU. The next two studies [ 72 4( a and b)] deal with chronic toxicity to aquatic fish and aquatic invertebrate species. EFED reserves the need for these studies pending completed ETU acute toxicity testing of freshwater and estuarine marine organisms. ETU has not triggered any risk based on acute freshwater fish and invertebrate testing with no LOCs exceeded for freshwater fish and invertebrates. EFED evaluated this ETU risk based on mancozeb's use pattern. ETU does not appear to be persistent in the aquatic environment. Quantities of ETU that reach or form in natural surfacewater are expected to be stable to hydrolysis/ direct photolysis, however, it was reported that ETU can be removed rather quickly from these waters by indirect photolysis ( half lives of 1 4 days)( Sue XU, 2000). EFED is reserving the requirement for Life Cycle Fish studies for both freshwater and estuarine or marine fish species ( guideline 72 5) awaiting the results of the Early Life Stage testing ( guideline 72 4a), if this study is needed. EFED still needs core studies to evaluate ETU's toxicity to aquatic plants [ guidelines 122 2 ( Tier I) or 123 2 ( Tier II)]. For a more detailed listing and explanation of ETU's hazards to aquatic organisms, see Appendix III. 38 Table VI 1: Toxicological Endpoints Used to Determine Aquatic Risk Quotients ( RQs) for ETU Type of Toxicity Organism Species Toxicological Endpoint Acute Freshwater fish rainbow trout ( Oncorhynchus mykiss) LC 50 > 502 ppm Chronic no data no data Acute Freshwater invertebrate waterflea ( Daphnia magna) LC 50 = 26.9 ppm Chronic no data no data Acute Estuarine/ marine fish no data no data Chronic no data no data Acute Estuarine/ marine invertebrate no data no data Chronic no data no data Acute Aquatic plant green algae ( Pseudokirchneriella subcapitata) EC 50 = 23 ppm b. Exposure and Risk Quotients EFED calculated surface water concentrations of ETU using the Pesticide Root Zone Model version 3.1.2 beta ( Carsel and others, 1997) and Exposure Analysis Modeling System version 2.98.04 ( Burns, 1997) ( PRZM EXAMS) for Tier II estimates ( see section V. Water Resource Assessment, for detailed explanation). EFED used the peak EECs to assess the acute risks to aquatic organisms from multiple applications.

EFED has limited aquatic toxicological data for ETU. However, the data available show that ETU does not exceed acute risk LOCs for freshwater fish, freshwater invertebrates or nonvascular aquatic plants. See tables 5, 6, and 7 in Appendix IV ( pages 72 75) for a detailed listing of the calculations and RQ results. EFED did not evaluate acute risks to estuarine and marine animals because of the lack of data. Through this document, EFED is requiring submission of this missing data. EFED does not perform chronic assessments to nontarget aquatic plants because EFED has not developed a risk scheme for assessing chronic risk to plants.

c. Aquatic Risk Assessment The limited ecotoxicological data for ETU shows ETU is a small acute toxicity risk to freshwater fish, freshwater invertebrates, and nonvascular aquatic plants with no LOCs exceeded. EFED has not received any adverse aquatic incidents reports about ETU. The study used to assess the risk to aquatic nonvascular plants is supplemental and EFED needs core data. EFED needs aquatic plant studies for a vascular aquatic plant, a marine diatom, a blue green algae and a freshwater diatom to evaluate fully ETU's risk to aquatic plants. EFED needs core studies to evaluate the acute risks to estuarine and marine organisms for ETU.

The EDBCs ( metiram, mancozeb, and maneb), unlike most pesticide active ingredients are not welldefined monomeric substances ( DÇtzer, 1994). The EDBCs are polymeric complexes and are nearly insoluble in water with a high affinity to adsorption by soil and sediment particles. The EBDC portion 39 that dissolves in water breaks up into a suite of transient ( that is, unpermanent or fleeting) chemical arrangements and degradates. This mix is no longer the parent material by itself but is consider to be EBDC complex. EBDC complex consists of transient species and degradates including the degradate of concern ETU. Over time ETU is an important transformation product of the EDBCs.

In contrast to the small risk ETU poses to freshwater fish, freshwater invertebrates, and nonvascular aquatic plants, with no LOCs exceeded, the EBDC complex which contain this degradate, show risk to freshwater fish, freshwater invertebrates, and nonvascular aquatic plants. The EBDCs' RQs for freshwater fish, freshwater invertebrates, and nonvascular aquatic plants exceed acute LOCs ( see individual chapters for mancozeb, metiram, and maneb). All the parent compounds exceed the acute aquatic LOCs for one or more use patterns while ETU does not exceed LOCs. Based on laboratory data and modeled EECs, the EBDC complex resulting from parent compounds are responsible for exceeding LOCs and not the common degradate, ETU. This means the EBDC portion that dissolves in water and breaks up into a suite of transient species and degradates, other than ETU, are responsible for the acute toxicity to freshwater fish, freshwater invertebrates, and nonvascular aquatic plants. EFED expects an early acute exposure risk to these aquatic organisms from the uses of the EBDC fungicides. This acute risk is caused by the EBDCs complex and is expected to disappear over time as the complex degrades rather quickly into ETU by hydrolytic reactions in aquatic environments. Because of this, EFED expects the acute toxicity to freshwater fish, freshwater invertebrates, and nonvascular aquatic plants, from exposure to the EBDC complexes, will not last long. The acute fish studies have a duration of 96 hours, while the acute invertebrate studies last 48 hours and the nonvascular aquatic plant studies are 120 hours in duration. Acceptable aquatic half life data is unavailable for most products of the EBDC complexes. EFED expects the parent EBDCs to hydrolyze quickly ( that is, within hours) to its complexes. Based on this information, EFED expects the EBDC complexes' acute toxicity to these aquatic organisms will last for 120 hours but suspects this toxicity will rapidly decline after this time period as these complexes degrade to ETU.

i. Incidents Based on information available in the Ecological Incident Information System ( EIIS), the Office of Pesticide Programs ( OPP) has not received any incident reports about adverse aquatic wildlife exposure to ETU. However, since ETU is a degradate of the EDBCs and not a pesticide, it is unlikely that OPP would receive incident reports for ETU. Filed incident reports would most likely be for one of the EBDCs, not specifically for ETU. See Appendix VI for description and background of EIIS.

ii. Endocrine Disruptors Based on limited ETU aquatic toxicological data, ETU does not appear to cause endocrine disrupting effects in the aquatic organisms tested. However, EFED cannot fully evaluate aquatic organisms for endocrine induced effects because of lack of data.

iii. Endangered Species At the current application rates and use patterns, ETU, as a degradate of the EDBC fungicides, is not likely to result in acute risks to endangered or threatened species of freshwater fish or invertebrates because no LOCs are exceeded. As pointed out in section VI. a.  Hazard Summary ( Acute/ Chronic), above, the Agency does not currently have data on which to evaluate the toxicity of ETU to endangered 19 The failure of one or more testes to descend into the scrotum.

40 or threatened species for all aquatic organisms groupings. Because of this, the risks to endangered or threatened species of some aquatic organisms from ETU exposure is uncertain. EFED is requiring the data to assess the risk to endangered or threatened species for these aquatic organism groupings through this document.

VII. Terrestrial Exposure and Risk a. Hazards Summary ( Acute/ Chronic)

EFED does not have any acute, subacute or chronic toxicity data to evaluate ETU's toxicity to birds. Because of this, EFED needs the Avian Acute Oral, Avian Acute Dietary, and Avian Reproduction studies [ guidelines 71 1( a), 71 2 ( a and b), and 71 4 ( a and b), respectively] for the TGAI of ETU.

ETU is practically nontoxic to small mammals from acute oral exposure ( LD 50 of 2,300 mg/ kg in tests done on laboratory mice). The Hazard Identification Assessment Review Committee ( HIARC) report ( 2003) concluded there were data gaps for a developmental toxicity study in rabbits and a 2 generation reproduction toxicity in rats. Results from a one dose developmental gavage study done on pregnant laboratory rats for ETU showed maternal and developmental toxicity at an LOAEL of 50 mg/ kg/ day. The study did not fix a NOAEL because this study used only one 50 mg/ kg/ day concentration. At this one dose concentration, developmental effects caused by ETU were gross developmental defects, central nervous system defects, skeletal deficiencies, cryptorchidism19, and decreased fetal weight. Other developmental effects caused by ETU were defects of the brain ( exencephaly, dilated ventricles, and hypoplastic cerebellum) in rats ( MRID No. 45937601). In this study, ETU was administered to rats by gavage. This study, in rats, resulted in a NOAEL of 5 mg/ kg/ day and a LOAEL of 10 mg/ kg/ day based on developmental toxicity. No maternal toxicity was noted in this study. To assess the chronic risks to mammals, EFED used MRID No. 45937601. In a 2 generation reproduction study ( MRID 42391701), ETU was administered to rats ( 25/ sex/ dose group) in diet at nominal dietary dose levels of 0, 2.5, 25, or 125 ppm. The F0 generation was treated for 70 days before mating and the F1 generation was treated 126 days before mating. EFED did not list or use this study because there was variability in dietary concentrations, feed spillage, stability problems with the test material, and unknown feed consumption. These uncertainties made calculating intake on a mg/ kg/ day basis impossible. There were also missing pups unaccounted for during the lactation period. The HIARC report ( 2003) classified this study as unacceptable. 41 Table VII 1: Mammalian Toxicity Mammalian Acute Oral Toxicity  ETU Species % ai LD 50 ( mg ai/ kg) Toxicity Category) Endpoints Affected MRID or Accession ( AC) No.

laboratory mouse ( Mus musculus) 98.0 2,300 ( female) practically nontoxic mortality not reported Mammalian Developmental Chronic Toxicity  ETU Species/ Study Duration % ai Test Type NOAEL/ LOAEL Toxicity Value ( mg/ kg/ day) Endpoints Affected MRID or Accession ( AC) No.

laboratory rat ( Rattus norvegicus) / not reported 99.0 Developmental not determined/ 50 mat.  decreased body wt. gain dev.  gross developmental defects, central nervous system defects, skeletal defects, cryptorchidism, and decreased fetal weight 00246663 laboratory rat ( Rattus norvegicus) / not reported/ not reported not reported Developmental 5/ 10 mat.  No maternal toxicity was noted in this study dev.  Based on developmental defects of the brain ( exencephaly, dilated ventricles, and hypoplastic cerebellum). 45937601 Khera, K. S.; Teratology 7: 243 252. 1973 EFED is not requiring insect testing of the degradate, ETU. The parent EBDCs are practically nontoxic to honeybees from short term contact exposure ( Guideline 141 1) and significant ETU exposure to honeybees in flight or while foraging on plants is unlikely. EFED believes any acute contact toxicity from ETU would have been expressed in the guideline testing of the parent EBDCs.

EFED has no toxicological data to settle the toxicity of ETU to terrestrial plants and limited data on the parent EBDC compounds. For the parent EBDC compounds, EFED has reviewed one core study ( MRID No. 44283401) which showed there was no phytotoxicity concerns. This study was an MAI TEP with mancozeb being one of two active ingredients. EFED is seeking an SAI TEP Tier I seedling emergence [ guideline 122 1( a)] and vegetative vigor [ guideline 122 1( b)] for the parent EBDC compounds ( mancozeb, metiram and maneb). Now, until EFED receives and reviews the testing results on the parent compounds, EFED is reserving the testing needs for the metabolite, ETU.

Table VII 2: Toxicological Endpoints Used to Determine Risk Quotients ( RQs) for ETU Type of Toxicity Organism Species Toxicological Endpoint Chronic Mammal laboratory rat ( Rattus norvegicus) NOAEL = 5 mg/ kg/ day1 1 LOAEL due to defects of the brain ( exencephaly, dilated ventricles, and hypoplastic cerebellum) in rats b. Exposure Summary 42 EFED evaluated terrestrial exposure using estimated environmental concentrations ( EECs) produced from the FATE version 5.0 model that calculates the decay of a chemical applied to foliar surfaces for single or multiple applications. The model assumes early concentrations on plant surfaces based on Kenaga predicted maximum and mean residues as adjusted by Fletcher and others. ( 1994) and assumes 1st order dissipation. Kenaga estimates and an explanation of the model with sample production are in Appendix II. The EECs modeled for ETU assumes 1.6 percent conversion on foliage of mancozeb to ETU as an estimate of exposure. EFED based the ETU EECs on the maximum application rate of mancozeb for the use patterns currently registered. EFED also assumed a 35 day total foliar residue dissipation half life for ETU in predicting EECs.

c. Risk Quotients Below ( figures VII 1 through VII 3) are graphs representing ETU's chronic risks to mammals. These graphs show the chronic RQs expected from mammals feeding on the food items listed. EFED calculated these chronic RQs from EECs based on the maximum Hoerger and Kenaga ( 1972) as modified by Fletcher and others ( 1994) residue estimates ( see Appendix II) of ETU on these food items following mancozeb's applications to various sites shown. ETU's RQs exceeded chronic LOCs for all mancozeb's uses. For small mammals ( 15 gram) feeding on short grass, the chronic RQs range from a high of 37 from mancozeb turf applications to 2 from mancozeb citrus applications. For medium sized mammals ( 35 gram) feeding on short grass, ETU's chronic RQ range from 26 for turf applications of mancozeb to 1 on citrus. For large mammals ( 1,000 gram) feeding on short grass, the RQs range from 6 on turf to 1 on bananas. There are no ETU chronic LOC exceedances to large mammals from mancozeb's use on potato & sugar beet, fennel, peanuts, forestry ( douglas fir), Christmas tree plantations, tobacco, cotton, asparagus, garlic & shallot, ornamentals, the barley crop grouping., vegetables or citrus. Because of this, Figure VII 3 does not show any bar charts for these sites since all the RQs are below the chronic LOC of 1. The RQs provided in figures VII 1 through VII 3 represents ETU's risk to various sized herbivore and insectivore mammals. EFED also calculated the RQs for granivore mammals. For mammalian granivores, no chronic LOC for ETU from mancozeb's uses was exceeded ( see Appendix IV, Table 4a for details).

EFED calculated the EECs for ETU's terrestrial exposure based on mancozeb's use pattern. EFED could have calculated RQs based on the use patterns of the other two parent compounds for ETU, metiram and maneb. EFED decided not to make these extra calculations since expected results would be the same and would only further confirm ETU's chronic risk to mammals. Also, mancozeb has the broadest use pattern ( most sites of application) and EFED expected mancozeb's uses would provide a more comprehensive view of the risks posed by ETU.

ETU effects triggering this chronic risk were based on developmental defects of the brain ( that is, exencephaly, dilated ventricles, and hypoplastic cerebellum) in rats from MRID 45937601. EFED used NOAELs from mammalian reproductive studies to calculate the chronic mamalian RQs for the parent EBDCs. These NOAELs resulted from dietary doses administered to rats. EFED used the NOAEL from a developmental study ( MRID 45937601) to calculate ETU's chronic risk to mammals. In this study, ETU was administered to rats by gavage. As a result, EFED needed to convert the NOAEL from this ETU developmental study to a dietary dose to estimate the ETU's chronic risk to mammals from mancozeb's use pattern. EFED calculated the RQs for three separate weight classes of mammals ( 15,35, and 1000 g) listed below ( figures VII 1 through VII 3) using the following equation: 43 RQ = EEC ( mg/ kg)/[ NOAEL ( mg/ kg bw/ day)/ %( decimal) Body Weight Consumed ( bw/ day)]

For more details and calculations of the ETU's chronic mammalian RQs, please see Appendix IV. 44 1 10 100 Risk Quotient Turf Ornamen Turf ( g Papaya Apples, Grapes Onion, Cranber Cucumbe Melons Tomato Corn ( E Bananas Corn ( W Potato Fennel Peanuts Forestr Christm Tobacco Grapes Cotton Asparag Ornamen Barley, Vegetab Citrus Mancozeb Application Sites Mammals Feeding on Short Grass Mammals Feeding on Forage & Small Inse Mammals Feeding on Large Insects ETU's Chronic Mammalian Risk Risk to Small Mammals ( 15 grams)

Figure VII 1 ETU Chronic Risk to Mammalian Herbivores & Insectivores RQ greater or equal to 1 exceeds chronic LOCs. Assumes degradation using Fate version 5.0 program with an ETU total foliar residue half life of 35 days and mancozeb to ETU conversion rate of 1.6% 45 1 10 100 Risk Quotient Turf Ornamen Turf ( g Papaya Apples, Grapes Onion, Cranber Cucumbe Melons Tomato Corn ( E Bananas Corn ( W Potato Fennel Peanuts Forestr Christm Tobacco Grapes Cotton Asparag Ornamen Barley, Vegetab Citrus Mancozeb Application Sites Mammals Feeding on Short Grass Mammals Feeding on Forage & Small Inse Mammals Feeding on Large Insects ETU's Chronic Mammalian Risk Risk to Medium Size Mammals ( 35 grams)

Figure VII 2 ETU Chronic Risk to Mammalian Herbivores & Insectivores RQ greater or equal to 1 exceeds chronic LOCs. Assumes degradation using Fate version 5.0 program with an ETU total foliar residue half life of 35 days and mancozeb to ETU conversion rate of 1.6% 46 1 10 100 Risk Quotient Turf Ornamen Turf ( g Papaya Apples, Grapes Onion, Cranber Cucumbe Melons Tomato Corn ( E Bananas Corn ( W Potato Fennel Peanuts Forestr Christm Tobacco Grapes Cotton Asparag Ornamen Barley, Vegetab Citrus Mancozeb Application Sites Mammals Feeding on Short Grass Mammals Feeding on Forage & Small Inse Mammals Feeding on Large Insects ETU's Chronic Mammalian Risk Risk to Large Mammals ( 1,000 grams)

Figure VII 3 ETU Chronic Risk to Mammalian Herbivores & Insectivores RQ greater or equal to 1 exceeds chronic LOCs. Assumes degradation using Fate version 5.0 program with an ETU total foliar residue half life of 35 days and mancozeb to ETU conversion rate of 1.6% 47 The acute risk from ETU exposure to terrestrial mammals, because of mancozeb's use, is expected to be a low risk since ETU is practically nontoxic to mammals ( mouse acute oral LD 50 = 2,300 mg/ kg). EFED did not calculate ETU acute RQs for mammals because of this low toxicity. For a more detailed listing and explanation of ETU's risk to mammals, see Appendix IV.

d. Terrestrial Risk Assessment Where will the ETU exposure come from when applicators treat plants with the parent EBDCs? ETU exposure will result from direct exposure on application because ETU is: ° in the formulation because of particle size decreases during the wet or dry milling; ° in the formulation as a result moisture exposure from unfavorable storage conditions; ° in the tank mix because of product dilution; or ° all three. ETU will also form from biodegradation when the EBDC parents meet with the soil. However, EFED expects the hydrolysis of the parent EBDCs will produce the greatest share of ETU before the EBDCs' complex binds to the soil particles. The parent EBDCs last briefly in the environment as shown in calculated half lives from registrant submitted, hydrolysis, studies. Except for applications to dry soils in dry environments, EFED expects a rapid change of the parent EBDCs into EBDC complex, including ETU; which is subjected to rapid degradation in aerobic soil systems.

How often will ETU exposure occur from the parent EBDCs' applications to plants? EFED presumes applications of the parent EBDC fungicides will occur when there is heavy plant disease pressure. Heavy disease pressure to plants results when there is high moisture from rains. These rains promote conditions for the growth and propagation of fungal species. EFED expects parent EBDC applications will result in rapid degradation of these parent EBDCs to ETU on plant surfaces. EFED figures the hydrolysis of the parent EDBCs will be variable but rather fast, that is, from one day to two weeks. EFED assumes rapid degradation will occur because the treated plants are likely to be either wet during the application or shortly after a parent EBDC application. The frequent applications of the parent EBDCs, in wet conditions, would provide a continuous exposure to EBDC complex including ETU. Physical wash off by rain and/ or irrigation is expected to play an important role in reducing exposure to the ETU part of the complex because of its high solubility.

Mammals are likely to be found in and around all mancozeb labeled sites. For example, producers grow tomatoes throughout the US, on both a commercial and noncommercial basis. Pesticide applicators apply around 860,000 lbs of mancozeb yearly to 49 % of the US planted, fresh tomatoes. ( EPA use data from 1992 through 2001)( BEAD's Quantitative Usage Analysis for Mancozeb dated November 1, 2002). Cottontail rabbits, deer, raccoons, opossums, skunks, woodchucks, muskrats, and groundhogs all feed on tomato plants. As well as feeding, some of these animals use areas in and around tomatoes for brood rearing, cover and loafing ( Gusey and Maturdo, 1973). The applications of mancozeb to tomatoes occur from seedling emergence ( spring) until 5 days before harvest ( in late summer or early fall) which coincides with the timing of the mammal pursuits mentioned. EFED expects mammalian exposure to ETU to be continuous during this time period. Even though EFED expects a continuous exposure to mammals from ETU, the developmental study used for ETU's chronic assessment endpoint results from a short term exposure. This means that even a single application could result in a potential chronic toxicity risk to mammals from ETU exposure. 48 i. Incidents Based on information available in the Ecological Incident Information System ( EIIS), the Office of Pesticide Programs ( OPP) has not received any incident reports about adverse wildlife exposure to ETU. However, since ETU is a degradate of the EDBCs and not a pesticide, it is unlikely that OPP would receive incident reports for ETU. Filed incident reports would most likely be for one of the parent EDBCs, not specifically for ETU. See Appendix VI for description and background of EIIS.

ii. Endocrine Disruptors The Federal Food, Drug, and Cosmetic Act ( FFDCA) requires EPA, as amended by the Food Quality Protection Act ( FQPA), to develop a screening program. This program is to decide whether certain substances ( including all pesticide active and other ingredients) " may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other such endocrine effects as the Administrator may designate." Following the recommendations of its Endocrine Disruptor Screening and Testing Advisory Committee ( EDSTAC), EPA determined there was scientific basis for including, as part of the program, the androgen and thyroid hormone systems, as well as the estrogen hormone system. EPA also adopted EDSTAC's recommendation including in the Program evaluations of potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA and FFDCA authority to require the wildlife evaluations. EPA will use FFDCA authority to evaluate effects in wildlife from tests that Food and Drug Administration uses to discover effects in humans. As the science develops and allows, EPA may add screening of more hormone systems to the Endocrine Disruptor Screening Program ( EDSP).

The mammalian feeding studies for ETU performed on rats and dogs ranged in time from 3 to 4 months. These feeding studies found the following effects: changes in thyroid hormones; changes in liver enzymes; microscopic changes in the liver and thyroids; increased thyroid weights; and increased relative liver weights. HED reviewed a one dose developmental gavage study done on pregnant laboratory rats. This study determined that treatment related developmental effects caused by ETU involved gross developmental defects, central nervous system defects, skeletal deficiencies, cryptorchidism ( failure of one or more testes to descend into the scrotum), and decreased fetal weight. See Appendix III for a detailed listing of the studies and results. These effects noted in mammals could be a result of hormonal disruptions and might suggest that ETU may be an endocrine disruptor. Based on these effects in mammals, EFED recommends that when EPA develops suitable screening and testing protocols, considered under the Agency's EDSP, ETU be subjected to more definitive testing to better characterize effects related to its endocrine disruption.

iii. Endangered Species Based on available screening level information there is a potential concern for chronic ETU effects on listed mammals should exposure actually occur. Chronic ETU RQs exceed LOCs for endangered and threatened species of mammals ( see Section c. Risk Quotients, above, for details). The Agency does not currently have data on which to evaluate the toxicity of ETU to endangered or threatened birds or terrestrial plants. Because of this, the risks to endangered or threatened species of birds and terrestrial plants from ETU exposure is uncertain. EFED is requiring the data to assess the risk to endangered or threatened species of birds through this document. EFED is reserving the terrestrial plant ETU data need awaiting a review of the parent EBDC's toxicity to terrestrial plants. 49 50 APPENDIX I: Additional Fate Data & Background for Models Used Adsorption/ desorption Data K ads data for ETU were also extracted from a laboratory technical report submitted by the registrant under MRID number 000971 58 ( Table IV 4). Data indicate high to medium mobility for ETU in most soils except Sassafras sandy loam and Cecil clay ( K oc ranges from 783 to 855) indicating low mobility.

Table IV 4. K ads and K oc and characteristics of the soils used in the adsorption/ desorption study ( MRID 000971 58)

Soil/ Sediment Type Solomon CL Virdan SiCL 1 Sassafras SL Hagerstown SiL Cecil Clay 2 Delaware River Sediment Textural class Clay Loam silty Clay loam Sandy Loam Silty Loam Clay Silt Clay (%) 32 18 6.0 28 54 8 pH ( water) 7.4 6.0 4.9 6.4 4.7 5.7 % Organic carbon 8.78 3.08 0.23 1.98 0.23 6.28 C. E. C ( meq/ 100g) 49.9 21.4 1.6 9.4 6.9 8.5 Kads ETU 5 9 2 3 2 29 Koc ETU 54 276 783 165 855 464 Kads Mancozeb3 32 49 18 4 50 101 Koc Mancozeb3 365 1,591 7,826 202 21,739 1,608 1 Montmorillonite Clay; 2 Kaolinite clay; 3 Mancozeb Study ( MRID 00888 22).

Background on Models Used in the Assessment Refer to Water MEMO ( Appendix VI) 51 APPENDIX II: Hoerger Kenaga Estimates & Fate v. 5.0 Model a. Hoerger Kenaga Estimates EFED uses Hoerger and Kenaga estimates ( 1972) as changed by Fletcher and other researchers ( 1994) to estimate the residues on plants and insects. Hoerger Kenaga categories represent preferred foods of various terrestrial vertebrates. Upland game birds prefer fruits and bud and shoot tips of leafy crops. Hares and hoofed mammals consume leaves and stems of leafy crops. Rodents consume seeds, seedpods and grasses; and various birds, mammals, reptiles and terrestrial phase amphibians consume insects. Terrestrial vertebrates also may contact pesticides applied to soil by swallowing pesticide granules or pesticide laden soil when foraging. Rich in minerals, soil comprises 5 to 30% of dietary intake by many wildlife species ( Beyer and Conner).

Hoerger and Kenaga based pesticide environmental concentration estimates on residue data correlated from more than 20 pesticides on more than 60 crops. These estimates are representative of many geographic regions ( 7 states) and a wide array of cultural practices. Hoerger Kenaga estimates also considered differences in vegetative yield, surface to mass ratio and interception causes. In 1994, Fletcher, Nellessen and Pfleeger reexamined the Hoerger Kenaga simple linear model ( y= B1x, where x= application rate and y= pesticide residue in ppm) to decide whether the terrestrial EEC's were accurate. They compiled a data set of pesticide day 0 and residue decay data involving 121 pesticides ( 85 insecticides, 27 herbicides, and 9 fungicides from 17 different chemical classes) on 118 species of plants. After analyzes, their conclusions were that Hoerger Kenaga estimates needed only minor changes to increase the predictive values. They recommended an increase for forage and fruit categories from 58 to 135 ppm and from 7 to 15 ppm, respectively. Otherwise, the Hoerger Kenaga estimates were accurate in predicting the maximum residue values after a 1 lb ai/ acre application. Mean values represent the arithmetic mean of values from samples collected the day of pesticide treatment. The values in the table below are the predicted 0 day maximum and mean residues of a pesticide that may occur on selected avian, mammalian, reptilian or terrestrial phase amphibian food items. These predicted residues occur immediately following a direct single application at a 1 lb ai/ acre application rate. For pesticides applied as a nongranular product ( for example, liquid or dust), EFED compared the estimated environmental concentrations ( EECs) on food items following product application to LC 50 values to assess risk. EFED based the estimated environmental concentrations of ETU on food items on Kenaga maximum and mean predicted values.

Estimated Environmental Concentrations on Avian and Mammalian Food Items ( ppm) Following a Single Application at 1 lb ai/ A)

Food Items EEC ( ppm) Predicted Maximum Residue1 EEC ( ppm) Predicted Mean Residue1 Short grass 240 85 Tall grass 110 36 Broadleaf/ forage plants and small insects 135 45 Fruits, pods, seeds, and large insects 15 7 1 Predicted maximum and mean residues are for a 1 lb ai/ a application rate and are based on Hoerger and Kenaga ( 1972) as modified by Fletcher et al. ( 1994).

b. Fate v. 5.0 Model Terrestrial Exposure Values 52 EFED calculated the exposure estimates of ETU to be a fraction of the exposure estimates for mancozeb. EFED modeled mancozeb labeled rates using FATE version 5.0 then multiplied the EECs by the 1.6% conversion rate.

The model assumes a first order decay to fix the concentration at each day after first application based on the concentration resulting from the first and more applications. The model calculates decay from the first order rate equation:

CT = Cie kT or in integrated form: ln ( CT/ Ci) =  kT Where: CT = concentration at time T on day zero Ci = concentration in parts per million ( ppm) present initially ( on day zero) on the surfaces. The model calculates Ci based on Kenaga and Fletcher by multiplying the application rate, in pounds active ingredient per acre. The model multiplies the application rate by 240 ( mean of 85) for short grass, 110 ( mean of 36) for tall grass, and 135 ( mean of 45) for broad leaf plants and insects and 15 ( mean of 7) for seeds. The model converts extra applications from pounds active ingredient per acre to PPM on the plant surface and the addition mass added to the mass of the chemical still present on the surfaces on the day of application.

k= degradation rate constant determined from studies of hydrolysis, photolysis, microbial degradation, etc. Since degradation rate is reported by half life, the model calculates the rate constant from the half life ( k = ln 2/ T1/ 2). Choosing the degradation rate and half life to use in terrestrial exposure calculations is open for debate and should be done by a qualified scientist.

T= time, in days, since the start of the simulation. The first application is on day 0. The simulation runs for the number of days entered by the modeler.

The program calculates concentration on each surface on a daily interval for the number of days entered by the modeler. The modeler chooses the days based on the guidance provided in Urban, 2000. The modeler uses the following formula with acute exposure addition of 30 days or the chronic exposure addition of 60 days:

maximum number of applications crop cycle or season minimum interval between applications ( days) + 30 or 60 days *

c. Fate v. 5.0 Model Sample Output for ETU Residues from Mancozeb's Use RUN No. 1 FOR MANCOZEB ON APPLES, ETC *** INPUT VALUES ***  RATE(#/ AC) APPLICATIONS HALF LIFE AVIAN ( ppm) MAMMALIAN ( mg/ kg) ONE( MAX) NO. INTERVAL ( DAYS) LC50 NOAEC LD50 NOAEL  4.800( 15.783) 4 7 35.0 ******* ******* ******* *******

MAXIMUM & 58 DAY AVERAGE KENAGA/ FLETCHER RESIDUES: 95th% ( mean) in ppm  SHORT BROADLEAF TALL SEED 53 GRASS & INSECTS GRASS FRUIT ____________________ ________________ ________________ ________________ MAX 3787.96( 1341.57) 2130.73( 710.24) 1736.15( 568.19) 236.75( 110.48)

RUN No. 2 FOR MANCOZEB ON ASPARAGUS *** INPUT VALUES ***  RATE(#/ AC) APPLICATIONS HALF LIFE AVIAN ( ppm) MAMMALIAN ( mg/ kg) ONE( MAX) NO. INTERVAL ( DAYS) LC50 NOAEC LD50 NOAEL  1.600( 4.873) 4 10 35.0 ******* ******* ******* *******

MAXIMUM & 70 DAY AVERAGE KENAGA/ FLETCHER RESIDUES: 95th% ( mean) in ppm  SHORT BROADLEAF TALL SEED GRASS & INSECTS GRASS FRUIT ____________________ ________________ ________________ ________________ MAX 1169.41( 414.16) 657.79( 219.26) 535.98( 175.41) 73.09( 34.11)

Below are lists of daily Kenaga Flether pesticide residue values for four avian/ mammalian food groupings for MANCOZEB use on TOMATO Values are in parts per million ( ppm).

SHORT BROADLEAF TALL SEED GRASS & INSECTS GRASS FRUIT DAILY DAILY DAILY DAILY VALUES VALUES VALUES VALUES DAY 95% MEAN 95% MEAN 95% MEAN 95% MEAN ___ _______________ _______________ _______________ _______________

1 576.00 204.00 324.00 108.00 264.00 86.40 36.00 16.80 2 564.71 200.00 317.65 105.88 258.82 84.71 35.29 16.47 3 553.63 196.08 311.42 103.81 253.75 83.04 34.60 16.15 4 542.78 192.23 305.31 101.77 248.77 81.42 33.92 15.83 5 532.13 188.46 299.32 99.77 243.89 79.82 33.26 15.52 6 521.70 184.77 293.45 97.82 239.11 78.25 32.61 15.22 7 511.47 181.14 287.70 95.90 234.42 76.72 31.97 14.92 8 1077.44 381.59 606.06 202.02 493.83 161.62 67.34 31.43 9 1056.31 374.11 594.17 198.06 484.14 158.45 66.02 30.81 10 1035.60 366.77 582.52 194.17 474.65 155.34 64.72 30.20 11 1015.29 359.58 571.10 190.37 465.34 152.29 63.46 29.61 12 995.38 352.53 559.90 186.63 456.22 149.31 62.21 29.03 13 975.86 345.62 548.92 182.97 447.27 146.38 60.99 28.46 14 956.72 338.84 538.16 179.39 438.50 143.51 59.80 27.90 15 1513.96 536.20 851.60 283.87 693.90 227.09 94.62 44.16 16 1484.28 525.68 834.91 278.30 680.29 222.64 92.77 43.29 17 1455.17 515.37 818.53 272.84 666.95 218.28 90.95 42.44 18 1426.63 505.27 802.48 267.49 653.87 214.00 89.16 41.61 19 1398.66 495.36 786.75 262.25 641.05 209.80 87.42 40.79 20 1371.23 485.64 771.32 257.11 628.48 205.68 85.70 39.99 21 1344.34 476.12 756.19 252.06 616.16 201.65 84.02 39.21 22 1893.98 670.79 1065.36 355.12 868.07 284.10 118.37 55.24 23 1856.84 657.63 1044.47 348.16 851.05 278.53 116.05 54.16 24 1820.43 644.74 1023.99 341.33 834.36 273.06 113.78 53.10 25 1784.73 632.09 1003.91 334.64 818.00 267.71 111.55 52.05 26 1749.74 619.70 984.23 328.08 801.96 262.46 109.36 51.03 27 1715.42 607.55 964.93 321.64 786.24 257.31 107.21 50.03 28 1681.79 595.63 946.00 315.33 770.82 252.27 105.11 49.05 29 2224.81 787.95 1251.45 417.15 1019.70 333.72 139.05 64.89 30 2181.18 772.50 1226.91 408.97 999.71 327.18 136.32 63.62 31 2138.41 757.35 1202.85 400.95 980.10 320.76 133.65 62.37 32 2096.48 742.50 1179.27 393.09 960.88 314.47 131.03 61.15 54 33 2055.36 727.94 1156.14 385.38 942.04 308.30 128.46 59.95 34 2015.06 713.67 1133.47 377.82 923.57 302.26 125.94 58.77 35 1975.55 699.67 1111.24 370.41 905.46 296.33 123.47 57.62 36 2512.81 889.95 1413.45 471.15 1151.70 376.92 157.05 73.29 37 2463.53 872.50 1385.74 461.91 1129.12 369.53 153.97 71.85 38 2415.22 855.39 1358.56 452.85 1106.98 362.28 150.95 70.44 39 2367.86 838.62 1331.92 443.97 1085.27 355.18 147.99 69.06 40 2321.43 822.17 1305.80 435.27 1063.99 348.21 145.09 67.71 41 2275.91 806.05 1280.20 426.73 1043.12 341.39 142.24 66.38 42 2231.28 790.24 1255.09 418.36 1022.67 334.69 139.45 65.08 43 2763.53 978.75 1554.48 518.16 1266.62 414.53 172.72 80.60 44 2709.33 959.56 1524.00 508.00 1241.78 406.40 169.33 79.02 45 2656.21 940.74 1494.12 498.04 1217.43 398.43 166.01 77.47 46 2604.12 922.29 1464.82 488.27 1193.55 390.62 162.76 75.95 47 2553.05 904.21 1436.09 478.70 1170.15 382.96 159.57 74.46 48 2502.99 886.48 1407.93 469.31 1147.20 375.45 156.44 73.00 49 2453.91 869.09 1380.32 460.11 1124.71 368.09 153.37 71.57 50 2405.79 852.05 1353.26 451.09 1102.65 360.87 150.36 70.17 51 2358.61 835.34 1326.72 442.24 1081.03 353.79 147.41 68.79 52 2312.36 818.96 1300.70 433.57 1059.83 346.85 144.52 67.44 53 2267.02 802.90 1275.20 425.07 1039.05 340.05 141.69 66.12 54 2222.56 787.16 1250.19 416.73 1018.67 333.38 138.91 64.82 55 2178.98 771.72 1225.68 408.56 998.70 326.85 136.19 63.55 56 2136.25 756.59 1201.64 400.55 979.12 320.44 133.52 62.31 57 2094.36 741.75 1178.08 392.69 959.92 314.15 130.90 61.09 58 2053.29 727.21 1154.98 384.99 941.09 307.99 128.33 59.89 59 2013.03 712.95 1132.33 377.44 922.64 301.95 125.81 58.71 60 1973.55 698.97 1110.12 370.04 904.55 296.03 123.35 57.56 61 1934.85 685.26 1088.35 362.78 886.81 290.23 120.93 56.43 62 1896.91 671.82 1067.01 355.67 869.42 284.54 118.56 55.33 63 1859.71 658.65 1046.09 348.70 852.37 278.96 116.23 54.24 64 1823.25 645.73 1025.58 341.86 835.65 273.49 113.95 53.18 65 1787.49 633.07 1005.47 335.16 819.27 268.12 111.72 52.14 66 1752.44 620.66 985.75 328.58 803.20 262.87 109.53 51.11 67 1718.08 608.49 966.42 322.14 787.45 257.71 107.38 50.11 68 1684.39 596.55 947.47 315.82 772.01 252.66 105.27 49.13 69 1651.36 584.86 928.89 309.63 756.87 247.70 103.21 48.16 70 1618.98 573.39 910.67 303.56 742.03 242.85 101.19 47.22 71 1587.23 562.14 892.82 297.61 727.48 238.08 99.20 46.29 72 1556.10 551.12 875.31 291.77 713.21 233.42 97.26 45.39 73 1525.59 540.31 858.14 286.05 699.23 228.84 95.35 44.50 74 1495.67 529.72 841.32 280.44 685.52 224.35 93.48 43.62 75 1466.34 519.33 824.82 274.94 672.07 219.95 91.65 42.77 76 1437.59 509.15 808.64 269.55 658.90 215.64 89.85 41.93 77 1409.40 499.16 792.79 264.26 645.97 211.41 88.09 41.11 78 1381.76 489.37 777.24 259.08 633.31 207.26 86.36 40.30 79 1354.67 479.78 762.00 254.00 620.89 203.20 84.67 39.51 80 1328.10 470.37 747.06 249.02 608.71 199.22 83.01 38.74 81 1302.06 461.15 732.41 244.14 596.78 195.31 81.38 37.98 82 1276.53 452.10 718.05 239.35 585.07 191.48 79.78 37.23 83 1251.49 443.24 703.97 234.66 573.60 187.72 78.22 36.50 84 1226.95 434.55 690.16 230.05 562.35 184.04 76.68 35.79 85 1202.89 426.02 676.63 225.54 551.33 180.43 75.18 35.08 86 1179.31 417.67 663.36 221.12 540.52 176.90 73.71 34.40 87 1156.18 409.48 650.35 216.78 529.92 173.43 72.26 33.72 88 1133.51 401.45 637.60 212.53 519.52 170.03 70.84 33.06 89 1111.28 393.58 625.10 208.37 509.34 166.69 69.46 32.41 90 1089.49 385.86 612.84 204.28 499.35 163.42 68.09 31.78 91 1068.13 378.29 600.82 200.27 489.56 160.22 66.76 31.15 92 1047.18 370.88 589.04 196.35 479.96 157.08 65.45 30.54 93 1026.65 363.60 577.49 192.50 470.55 154.00 64.17 29.94 55 94 1006.51 356.47 566.16 188.72 461.32 150.98 62.91 29.36 95 986.78 349.48 555.06 185.02 452.27 148.02 61.67 28.78 96 967.43 342.63 544.18 181.39 443.40 145.11 60.46 28.22 97 948.46 335.91 533.51 177.84 434.71 142.27 59.28 27.66 98 929.86 329.32 523.04 174.35 426.18 139.48 58.12 27.12 99 911.62 322.87 512.79 170.93 417.83 136.74 56.98 26.59 100 893.75 316.54 502.73 167.58 409.63 134.06 55.86 26.07 101 876.22 310.33 492.87 164.29 401.60 131.43 54.76 25.56 102 859.04 304.24 483.21 161.07 393.73 128.86 53.69 25.06 103 842.19 298.28 473.73 157.91 386.01 126.33 52.64 24.56 104 825.68 292.43 464.44 154.81 378.44 123.85 51.60 24.08 105 809.49 286.69 455.34 151.78 371.02 121.42 50.59 23.61 106 793.61 281.07 446.41 148.80 363.74 119.04 49.60 23.15 107 778.05 275.56 437.65 145.88 356.61 116.71 48.63 22.69 108 762.79 270.16 429.07 143.02 349.61 114.42 47.67 22.25 109 747.84 264.86 420.66 140.22 342.76 112.18 46.74 21.81 110 733.17 259.67 412.41 137.47 336.04 109.98 45.82 21.38 111 718.79 254.57 404.32 134.77 329.45 107.82 44.92 20.96 112 704.70 249.58 396.39 132.13 322.99 105.70 44.04 20.55 113 690.88 244.69 388.62 129.54 316.65 103.63 43.18 20.15 114 677.33 239.89 381.00 127.00 310.44 101.60 42.33 19.76 115 664.05 235.18 373.53 124.51 304.36 99.61 41.50 19.37 116 651.03 230.57 366.20 122.07 298.39 97.65 40.69 18.99 117 638.26 226.05 359.02 119.67 292.54 95.74 39.89 18.62 118 625.75 221.62 351.98 117.33 286.80 93.86 39.11 18.25 119 613.48 217.27 345.08 115.03 281.18 92.02 38.34 17.89 120 601.45 213.01 338.31 112.77 275.66 90.22 37.59 17.54 121 589.65 208.84 331.68 110.56 270.26 88.45 36.85 17.20 122 578.09 204.74 325.18 108.39 264.96 86.71 36.13 16.86 123 566.75 200.73 318.80 106.27 259.76 85.01 35.42 16.53 124 555.64 196.79 312.55 104.18 254.67 83.35 34.73 16.21 125 544.74 192.93 306.42 102.14 249.67 81.71 34.05 15.89 126 534.06 189.15 300.41 100.14 244.78 80.11 33.38 15.58 127 523.59 185.44 294.52 98.17 239.98 78.54 32.72 15.27 128 513.32 181.80 288.74 96.25 235.27 77.00 32.08 14.97 129 503.26 178.24 283.08 94.36 230.66 75.49 31.45 14.68 130 493.39 174.74 277.53 92.51 226.14 74.01 30.84 14.39 131 483.71 171.32 272.09 90.70 221.70 72.56 30.23 14.11 132 474.23 167.96 266.75 88.92 217.35 71.13 29.64 13.83 133 464.93 164.66 261.52 87.17 213.09 69.74 29.06 13.56 134 455.81 161.43 256.39 85.46 208.91 68.37 28.49 13.29 135 446.87 158.27 251.37 83.79 204.82 67.03 27.93 13.03 136 438.11 155.16 246.44 82.15 200.80 65.72 27.38 12.78 137 429.52 152.12 241.60 80.53 196.86 64.43 26.84 12.53 138 421.10 149.14 236.87 78.96 193.00 63.16 26.32 12.28 139 412.84 146.21 232.22 77.41 189.22 61.93 25.80 12.04 140 404.74 143.35 227.67 75.89 185.51 60.71 25.30 11.81 141 396.81 140.54 223.20 74.40 181.87 59.52 24.80 11.57 142 389.03 137.78 218.83 72.94 178.30 58.35 24.31 11.35 143 381.40 135.08 214.54 71.51 174.81 57.21 23.84 11.12 144 373.92 132.43 210.33 70.11 171.38 56.09 23.37 10.91 145 366.59 129.83 206.20 68.73 168.02 54.99 22.91 10.69 146 359.40 127.29 202.16 67.39 164.72 53.91 22.46 10.48 147 352.35 124.79 198.20 66.07 161.49 52.85 22.02 10.28 148 345.44 122.34 194.31 64.77 158.33 51.82 21.59 10.08 149 338.67 119.94 190.50 63.50 155.22 50.80 21.17 9.88 150 332.03 117.59 186.76 62.25 152.18 49.80 20.75 9.68 151 325.51 115.29 183.10 61.03 149.19 48.83 20.34 9.49 152 319.13 113.03 179.51 59.84 146.27 47.87 19.95 9.31 153 312.87 110.81 175.99 58.66 143.40 46.93 19.55 9.13 154 306.74 108.64 172.54 57.51 140.59 46.01 19.17 8.95 56 155 300.72 106.51 169.16 56.39 137.83 45.11 18.80 8.77 156 294.83 104.42 165.84 55.28 135.13 44.22 18.43 8.60 157 289.05 102.37 162.59 54.20 132.48 43.36 18.07 8.43 158 283.38 100.36 159.40 53.13 129.88 42.51 17.71 8.27 159 277.82 98.39 156.27 52.09 127.33 41.67 17.36 8.10 160 272.37 96.47 153.21 51.07 124.84 40.86 17.02 7.94 161 267.03 94.57 150.21 50.07 122.39 40.05 16.69 7.79 162 261.80 92.72 147.26 49.09 119.99 39.27 16.36 7.64 163 256.66 90.90 144.37 48.12 117.64 38.50 16.04 7.49 164 251.63 89.12 141.54 47.18 115.33 37.74 15.73 7.34 165 246.69 87.37 138.77 46.26 113.07 37.00 15.42 7.20 166 241.86 85.66 136.04 45.35 110.85 36.28 15.12 7.05 167 237.11 83.98 133.38 44.46 108.68 35.57 14.82 6.92 168 232.46 82.33 130.76 43.59 106.55 34.87 14.53 6.78 169 227.91 80.72 128.20 42.73 104.46 34.19 14.24 6.65 170 223.44 79.13 125.68 41.89 102.41 33.52 13.96 6.52 171 219.06 77.58 123.22 41.07 100.40 32.86 13.69 6.39 172 214.76 76.06 120.80 40.27 98.43 32.21 13.42 6.26 173 210.55 74.57 118.43 39.48 96.50 31.58 13.16 6.14 174 206.42 73.11 116.11 38.70 94.61 30.96 12.90 6.02 175 202.37 71.67 113.83 37.94 92.75 30.36 12.65 5.90 176 198.40 70.27 111.60 37.20 90.93 29.76 12.40 5.79 177 194.51 68.89 109.41 36.47 89.15 29.18 12.16 5.67 178 190.70 67.54 107.27 35.76 87.40 28.60 11.92 5.56 179 186.96 66.21 105.16 35.05 85.69 28.04 11.68 5.45 180 183.29 64.92 103.10 34.37 84.01 27.49 11.46 5.35 181 179.70 63.64 101.08 33.69 82.36 26.95 11.23 5.24 182 176.17 62.40 99.10 33.03 80.75 26.43 11.01 5.14 183 172.72 61.17 97.16 32.39 79.16 25.91 10.80 5.04 184 169.33 59.97 95.25 31.75 77.61 25.40 10.58 4.94 185 166.01 58.80 93.38 31.13 76.09 24.90 10.38 4.84 186 162.76 57.64 91.55 30.52 74.60 24.41 10.17 4.75 187 159.57 56.51 89.76 29.92 73.13 23.93 9.97 4.65 188 156.44 55.40 88.00 29.33 71.70 23.47 9.78 4.56 189 153.37 54.32 86.27 28.76 70.29 23.01 9.59 4.47 190 150.36 53.25 84.58 28.19 68.92 22.55 9.40 4.39 191 147.41 52.21 82.92 27.64 67.56 22.11 9.21 4.30 192 144.52 51.19 81.29 27.10 66.24 21.68 9.03 4.22 193 141.69 50.18 79.70 26.57 64.94 21.25 8.86 4.13 194 138.91 49.20 78.14 26.05 63.67 20.84 8.68 4.05 195 136.19 48.23 76.60 25.53 62.42 20.43 8.51 3.97 196 133.52 47.29 75.10 25.03 61.19 20.03 8.34 3.89 197 130.90 46.36 73.63 24.54 59.99 19.63 8.18 3.82 198 128.33 45.45 72.19 24.06 58.82 19.25 8.02 3.74 199 125.81 44.56 70.77 23.59 57.66 18.87 7.86 3.67 200 123.35 43.69 69.38 23.13 56.53 18.50 7.71 3.60 ___ _______________ _______________ _______________ _______________ SHORT BROADLEAF TALL SEED GRASS & INSECTS GRASS FRUIT AVERAGE AVERAGE AVERAGE AVERAGE VALUES VALUES VALUES VALUES DAY 95% MEAN 95% MEAN 95% MEAN 95% MEAN ___ _______________ _______________ _______________ _______________ 997.24 353.19 560.95 186.98 457.07 149.59 62.33 29.09 57 APPENDIX III: Ecological Hazards Assessment a. Review ETU is a degradate of toxicological concern in mammals. Because ETU is a common degradate of mancozeb, metiram, and maneb, EFED is providing the hazards assessment for ETU in this section rather than providing redundant information in each of the REDs for mancozeb, metiram, and maneb.

b. Toxicity to Terrestrial Animals i. Birds, Acute, Subacute and Chronic EFED does not have any acute, subacute or chronic toxicity data to evaluate ETU's toxicity to birds. Because of this, EFED needs the Avian Acute Oral, Avian Acute Dietary, and Avian Reproduction studies [ guidelines 71 1( a), 71 2 ( a and b), and 71 4 ( a and b), respectively] for the TGAI of ETU.

ii. Mammals, Acute and Chronic 1. Acute Oral EFED needs for wild mammal testing depends on the results of lower tier laboratory mammalian studies, intended use pattern and environmental fate characteristics. Usually, rat or mouse toxicity values received from the Agency's Health Effects Division ( HED) substitute for wild mammal testing. EFED took the toxicity values used in this assessment ( see tables that follow) from HED. This assessment used HED's Tox One Liner, preliminary draft reports received in October, 1999 and the final Hazard Identification Assessment Review Committee ( HIARC) reports on ETU dated November 16, 1999, December 18, 2001, and May 28, 2003. This assessment will use the toxicity values ( LD 50 and NOAEL) appearing in the shaded areas of the tables to calculate the acute and chronic mammalian risk quotients ( RQ's) in later sections. Toxicity category descriptions are the following ( Brooks, 1973):

If the LD 50 is less than 10 mg a. i./ kg, then the test substance is very highly toxic. If the LD 50 is 10 to 50 mg a. i./ kg, then the test substance is highly toxic. If the LD 50 is 51 to 500 mg a. i./ kg, then the test substance is moderately toxic. If the LD 50 is 501 to 2,000 mg a. i./ kg, then the test substance is slightly toxic. If the LD 50 is greater than 2,000 mg a. i./ kg, then the test substance is practically nontoxic.

The results show that ETU is practically nontoxic to mammals from acute oral exposure ( Table 1).

Table 1: Mammalian Acute Oral Toxicity  ETU Species % ai LD 50 ( mg ai/ kg) Toxicity Category) Endpoints Affected MRID or Accession ( AC) No.

laboratory mouse ( Mus musculus) 98.0 2,300 ( female) practically nontoxic mortality not reported 20 The failure of one or more testes to descend into the scrotum.

58 2. Acute Dermal and Inhalation Toxicity Testing The HED reports provided no acute dermal or inhalation endpoints for ETU.

3. Mammalian Subchronic Toxicity Testing Table 2 shows various mammalian subchronic feeding studies. The 96.8% ai listing in Table 2 shows a 3 month dietary exposure to ETU at a 25 ppm level will cause thyroid hyperplasia in mammals. Thyroid hyperplasia is an increase in the number of thyroid cells causing and enlargement of the thyroid.

Table 2: Mammalian Subchronic Toxicity  ETU Surrogate Species/ % ai NOAEL/ LOAEL ( mg/ kg/ day) LOAEL Endpoints MRID or Accession ( AC) No.

Laboratory rat ( Rattus norvegicus)/ feeding 3 months 99.8 not determined/ 14.28 ( n/ a/ 250 ppm) 1 body weight decrements, changes in thyroid hormones, changes in liver enzymes, microscopic changes in the liver and thyroids, increased absolute and relative thyroid weights, and increased relative liver weights 00261536 Domestic dog ( Canis familiaris)/ feeding 13 weeks 98.0 6.25/ 66.23 ( 150.0/ 2000.0 ppm) 1 severe thyroid and pituitary hypertrophy ( and death of two males); increased cholesterol and reduced T4/ T3 in both sexes not reported Laboratory rat ( Rattus norvegicus)/ feeding 4 months not reported < 50.0/ 50.0 ppm1 increased thyroid weights not reported Laboratory rat ( Rattus norvegicus)/ feeding 3 months 96.8 5.0/ 25.0 ppm1 thyroid hyperplasia not reported Laboratory rat ( Rattus norvegicus)/ feeding 3 months not reported < 60.0/ 60.0 ppm1 hepatoctic cellular atypia ( abnormal liver cells) AC259905 Laboratory mouse ( Mus musculus)/ feeding 3 months not reported 1.72/ 18.18 ( 10/ 100 ppm) 1 thyroid follicular cell hypertrophy or hyperplasia AC2598882 1 ppm results provided in study 2 HED classified this study " unacceptable/ guideline." This study does not satisfy guideline requirements for a subchronic oral study in mice with ethylene thiourea because the authors failed to report the % purity and dietary concentrations of ETU. An upgrade in the study classification of the ethylene thiourea portion of the study is achievable if the authors report these data.

4. Mammalian Reproductive & Developmental Toxicity Testing The HIARC report ( 2003) concluded there were data gaps for a developmental toxicity study in rabbits and a 2 generation reproduction toxicity in rats.

Developmental effects caused by ETU were gross developmental defects, central nervous system defects, skeletal deficiencies, cryptorchidism20, and decreased fetal weight ( see MRID No. 00246663). This particular study also determined endpoints for the parent, mancozeb ( see Appendix III for mancozeb RED). Although mancozeb and ETU caused many of the same developmental effects, ETU 59 caused these effects at a much lower level ( 50 mg/ kg/ day or1000 ppm) compared to mancozeb ( 512 mg/ kg/ day or10,240 ppm). In this rat developmental study, the authors gave 50 mg/ kg/ day of ETU to a single dose group of pregnant rats by gavage from days 6 15 of gestation. The affected endpoints occurred at this one dose level, resulting in an indecisive NOAEL. Other developmental effects caused by ETU were defects of the brain ( exencephaly, dilated ventricles, and hypoplastic cerebellum) in rats ( MRID No. 45937601). In this study, ETU was administered to rats by gavage at doses of 0, 5, 10, 20, 40, or 80 ( group II only) mg/ kg/ day. There were 3 treatment groups: Group I was treated from 21 42 days before mating until gestation day ( GD) 15, Group II was treated from GD 6 15, and Group III from GD 7 20. No maternal toxicity was noted in this study and the NOAEL for maternal toxicity is 80 mg/ kg/ day, the highest dose tested. The LOAEL for maternal toxicity was not determined. The NOAEL for developmental toxicity is 5 mg/ kg/ day and the LOAEL is 10 mg/ kg/ day based on developmental defects of the brain ( exencephaly, dilated ventricles, and hypoplastic cerebellum). To assess the chronic risks to mammals, EFED will be using MRID No. 45937601.

In a 2 generation reproduction study ( MRID 42391701), ETU was administered to rats ( 25/ sex/ dose group) in diet at nominal dietary dose levels of 0, 2.5, 25, or 125 ppm. The F0 generation was treated for 70 days before mating and the F1 generation was treated 126 days before mating. EFED did not list or use this study because there was variability in dietary concentrations, feed spillage, stability problems with the test material, and unknown feed consumption. These uncertainties made calculating intake on a mg/ kg/ day basis impossible. There were also missing pups unaccounted for during the lactation period. The HIARC report ( 2003) classified this study as unacceptable.

A long term ( 1 year) feeding study on dogs resulted in decreased body weight gain, enlarged thyroid with follicular dilation and hypertrophy at a 50 ppm ETU exposure level. At a 5.0 ppm exposure level, ETU effects in rats, from 1 2 year feeding studies, resulted in enlarged thyroids.

Table 3: Mammalian Feeding, Developmental and Reproductive Chronic Toxicity  ETU Species/ Study Duration % ai Test Type NOAEL/ LOAEL Toxicity Value ( mg/ kg/ day) Endpoints Affected MRID or Accession ( AC) No.

laboratory rat ( Rattus norvegicus) / not reported 99.0 Developmental not determined/ 50 ( not determined/ 1000 ppm) 1 ( maternal & developmental) extrapolated NOAEL= 0.05 mg/ kg/ day or 1 ppm1 using UFs mat.  decreased body wt. gain dev.  gross developmental defects, central nervous system defects, skeletal defects, cryptorchidism, and decreased fetal weight 00246663 laboratory rat ( Rattus norvegicus) / not reported/ not reported not reported Developmental 5/ 10 ( 100/ 200 ppm) 1 mat.  No maternal toxicity was noted in this study dev.  Based on developmental defects of the brain ( exencephaly, dilated ventricles, and hypoplastic cerebellum). 45937601 Khera, K. S.; Teratology 7: 243 252. 1973 Domestic dog ( Canis familiaris)/ 1 year 98.0 Feeding 0.185/ 1.89 ( 5.0/ 50.0 ppm) 2 decreased body weight gain, enlarged thyroid, accompanied by follicular dilation and hypertrophy 42338101 Laboratory rat ( Rattus norvegicus) / 1 year not reported Feeding < 5.0/ 5.0 ppm increased vascularity of the thyroid AC259905 Table 3: Mammalian Feeding, Developmental and Reproductive Chronic Toxicity  ETU Species/ Study Duration % ai Test Type NOAEL/ LOAEL Toxicity Value ( mg/ kg/ day) Endpoints Affected MRID or Accession ( AC) No.

60 laboratory rat ( Rattus norvegicus) / 2 year 96.2 Feeding 0.17 / 0.37 ( male) 2.5/ 5.0 ppm2 diffuse follicular hyperplasia of the thyroid gland and round cell infiltration of the lungs in males at week 52 not reported laboratory rat ( Rattus norvegicus) / 2 year not reported Feeding < 5.0/ 5.0 ppm thyroid follicular cell hyperplasia AC259905 1 ppm conversion based on: 1 mg/ kg/ day = 20 ppm in adult rats. ( Nelson, 1975) 2 ppm results provided in study iii. Insect Acute Contact EFED is not requiring insect testing of the degradate, ETU. The parent EBDCs are practically nontoxic to honeybees from short term contact exposure ( Guideline 141 1) and significant ETU exposure to honeybees in flight or while foraging on the nectar or pollen producing parts of plants is unlikely. ETU results from both the initial rapid hydrolysis of parent EBDCs and the slow, continuous degradation of the parent EBDCs in soil and sediment.

iv. Terrestrial Field Testing EFED is not needing terrestrial field testing for ETU and registrants have not filed any ETU terrestrial field studies for review.

c. Toxicity to Aquatic Organism Preface EFED has limited acute toxicity data to evaluate ETU's toxicity to aquatic organisms. EFED is requiring submission of or reserving the need for the following guidelines studies:

72 1( a) Acute Fish Toxicity Bluegill a freshwater fish dwelling in warm waters 72 3( a) Acute Estuarine/ Marine Toxicity Fish 72 3( b) Acute Estuarine/ Marine Toxicity Mollusk 72 3( c) Acute Estuarine/ Marine Toxicity Shrimp 72 4( a) Early Life Stage Fish for freshwater and estuarine/ marine species 72 4( b) Life Cycle Aquatic Invertebrate for freshwater and estuarine/ marine species EFED needs submission of these studies for the TGAI of ETU. The first study listed above [ 72 1( a)] is a basic study need for all pesticides. EFED is requiring this study for ETU because ETU is a degradate toxic to mammals which may be toxic to aquatic wildlife. The next three studies [ 72 3( a, b, and c)], deal with the acute toxicity to estuarine and marine species. EFED needs these studies because of the EBDCs' use in coastal counties where EFED expects estuarine or marine exposure to the EBDCs and their common degradate, ETU. The next two studies [ 72 4( a and b)] deal with chronic 61 toxicity to aquatic fish and aquatic invertebrate species. EFED reserves the need for these studies pending completed ETU acute toxicity testing of freshwater and estuarine marine organisms. ETU has not triggered any risk based on acute freshwater fish and invertebrate testing with no LOCs exceeded for freshwater fish and invertebrates. EFED evaluated this ETU risk based on mancozeb's use pattern. ETU does not appear to be persistent in the aquatic environment. Quantities of ETU that reach or form in natural surface water are expected to be stable to hydrolysis/ direct photolysis, however, it was reported that ETU can be removed rather quickly from these waters by indirect photolysis ( half lives of 1 4 days) ( Sue XU, 2000). EFED is reserving the requirement for Life Cycle Fish studies for both freshwater and estuarine or marine fish species ( guideline 72 5) awaiting the results of the Early Life Stage testing ( guideline 72 4a), if this study is needed.

i. Toxicity to Freshwater Animals 1. Freshwater Fish, Acute The Agency requires two freshwater fish toxicity studies using the TGAI to find out the toxicity of ETU to fish. The preferred test species are rainbow trout ( a cold water fish, Guideline 72 1c) and bluegill sunfish ( a warm water fish; Guideline 72 1a). Tabulated below, are results of the rainbow trout test. The toxicity category descriptions for freshwater and estuarine or marine fish and aquatic invertebrates, are below in parts per million ( ppm), the standard units of measure ( Brooks, 1973). EFED will use the toxicity values ( LC 50 ) appearing in the shaded area of the tables to calculate the acute aquatic risk quotients ( RQ's).

If the LC 50 is less than 0.1 ppm a. i., then the test substance is very highly toxic. If the LC 50 is 0.1 to 1.0 ppm a. i., then the test substance is highly toxic. If the LC 50 is greater than 1 and up through 10 ppm a. i., then the test substance is moderately toxic. If the LC 50 is greater than 10 and up through 100 ppm a. i., then the test substance is slightly toxic. If the LC 50 is greater than 100 ppm a. i., then the test substance is practically nontoxic.

Based on acute exposure, ETU is practically nontoxic to cold water fish ( rainbow trout LC 50 > 502 ppm based on measured samples) ( see Table 4, below). MRID No. 45910401 ( duplicate MRID No. 46020903) fulfills the guideline 72 1( c) need. EFED needs a core freshwater fish study for a warm water fish to fulfill guideline 72 1( a).

Table 4: Freshwater Fish 96 hr Acute Toxicity  ETU Technical Species/ Flow through or Static/ Duration % ai LC50 / ( ppm ai)/ ( measured/ nominal) Toxicity Category MRID / Accession No./ Author/ Year Study Classification1 Rainbow Trout ( Oncorhynchus mykiss)/ static/ 96 hour 99.9 > 502 ( measured) practically nontoxic 45910401 or 46020903/ Zok, S./ 2001 Core 2. Freshwater Invertebrates, Acute The Agency requires a freshwater aquatic invertebrate toxicity test using the TGAI to find out the acute toxicity of ETU to aquatic invertebrates. The preferred test organism is Daphnia magna, but early instar amphipods, stoneflies, mayflies, or midges are also acceptable. A core acute daphnid study ( MRID No. 45910402) shows ETU's freshwater aquatic invertebrates EC 50 value is 26.9 ppm based on measured samples. Tabulated below ( Table 5) are the results of this test. MRID No. 45910402 62 ( duplicate MRID No. 46020901) fulfills the guideline 72 2( a) need.

Table 5: Freshwater Invertebrate Acute Toxicity  Metiram Technical Species/ Static or Flowthrough Duration % ai LC50/ EC50 ( ppm)/ ( nominal/ measured) Toxicity Category MRID/ Accession ( AC) No. Author/ Year Study Classification1 Daphnid ( Daphnia magna)/ static ( 48 hr.) 99.6 26.9 ( measured) slightly toxic 45910402 or 46020901/ Hisgen/ 2000 Core 1 Core ( study satisfies guideline). Supplemental ( study is scientifically sound, but does not satisfy guideline)

ii. Aquatic Field Studies EFED reviewed a draft freshwater simulated aquatic field study ( MRID No. 44944401) in February 2000. The Mancozeb RED contains a shortened review of this field study. The authors of the study initially tried to base the results on measured concentrations of ETU since they expected a 2 to 14 hour mancozeb half life in an aquatic environment. The authors were unable to base their results on measured concentrations of ETU because they could not analytically detect ETU at the low levels needed. Because of this, the authors based the results of the study on nominal concentrations of mancozeb. This study did not provide any useful information on the toxicological effects of ETU in a freshwater ecosystem.

d. Toxicity to Plants i. Terrestrial Plants EFED has no toxicological data to settle the toxicity of ETU to terrestrial plants and limited data on the parent EBDC compounds. For the parent EBDC compounds, EFED has reviewed one core study ( MRID No. 44283401) which showed there was no phytotoxicity concerns. This study was an MAI TEP with mancozeb being one of two active ingredients. EFED is seeking an SAI TEP Tier I seedling emergence [ guideline 122 1( a)] and vegetative vigor [ guideline 122 1( b)] for the parent EBDC compounds ( mancozeb, metiram and maneb). Now, until EFED receives and reviews the testing results on the parent compounds, EFED is reserving the testing needs for the metabolite, ETU.

ii. Aquatic Plants ETU does not appear to be persistent in the aquatic environment. Quantities of ETU that reach or form in natural surface water are expected to be stable to hydrolysis/ direct photolysis, however, it was reported that ETU can be removed rather quickly from these waters by indirect photolysis ( half lives 63 of 1 4 days) ( Sue XU, 2000). However ETU is the major degradate of all three EBDC compounds, and the EBDCs rapidly breakdown to ETU in aquatic environments. Because of this, EFED is recommending Tier I ( guideline 122 2) or Tier II ( guideline 123 2) aquatic plant testing for ETU. Tier I aquatic plant testing is a maximum dose test designed to evaluate the toxic effects to the test species in growth and reproduction. The result of Tier I testing decides the need for more aquatic plant testing. Tier II aquatic plant testing is a multiple dose test of the plants species that showed a phytotoxic effect to the pesticide at the Tier I level. Tier II testing fixes the harmful effect levels of the chemical on the aquatic plants which showed a greater than 50% damaging effect in Tier I testing.

For ETU, EFED reviewed one Tier II supplemental study for Pseudokirchneriella subcapitata ( formerly Selenastrum capricornutum), a freshwater green alga. EFED tabulated results of Tier II toxicity testing on the technical material in Table 6, below. The EC 50 for Pseudokirchneriella subcapitata was 23.0 ppm a. i. based on a decline in cell density; the NOAEC was 12.5 ppm. EFED classified MRID No. 45910403 ( duplicate MRID No. 46020902) as supplemental because the test duration was only 72 hours and the guidelines require the test duration to be 120 hours. EFED will use the toxicity value ( EC 50 ) appearing in the shaded area of the table to calculate the acute risk quotients ( RQ's) in later sections. EFED still needs core studies to evaluate ETU's toxicity to aquatic plants. EFED needs core Tier I or Tier II aquatic plant growth studies for duckweed ( Lemna gibba), marine diatom ( Skeletonema costatum), blue green algae ( Anabaena flos aquae), freshwater green alga ( Selenastrum capricornutum), and a freshwater diatom.

Table 6: Nontarget Aquatic Plant Toxicity ( Tier II)  ETU Species/ duration % A. I. EC50/ NOAEC ( ppm ai) MRID No. Author/ year Classification1 Nonvascular Plants freshwater green algae ( Pseudokirchneriel la subcapitata) / 72 hrs. 99.6 23.0/ 12.5 ( measured) 45910403 or 46020902/ Reuschenbach/ 2000 Supplemental 1 Core ( study satisfies guideline). Supplemental ( study is scientifically sound, but does not satisfy guideline).

iii. Aquatic Plant Field Studies EFED is not seeking aquatic plant field testing for ETU and registrants have not filed any ETU aquatic plant field studies for review. 64 APPENDIX IV: Environmental Exposure Assessment a. Review of Risk Quotients ( RQs)

Risk characterization integrates the results of the exposure and ecotoxicity data to evaluate the likelihood of adverse ecological effects. The Agency calls this integration the quotient method. The Agency calculates risk quotients ( RQs) by dividing exposure estimates by acute and chronic ecotoxicity values.

RQ = EXPOSURE/ TOXICITY EFED compares RQs to OPP's levels of concern ( LOCs). OPP uses these LOCs to analyze potential risk to nontarget organisms and the need to consider regulatory action. This method signals that a pesticide used as directed has the potential to cause adverse effects on nontarget organisms. LOCs currently address the following risk presumption categories: ( 1) acute risks  the risks warrant regulatory action as well as restricted use classification; ( 2) acute restricted use  the potential for acute risk exists, but the restricted use classification may mitigate the risk; ( 3) acute endangered species  the risk may adversely affect endangered; and ( 4) chronic risk  the risk may warrant regulatory action because there is a potential for chronic risk. Currently, EFED does not perform assessments for chronic risk to plants, acute or chronic risks to nontarget insects, or chronic risk from granular or bait formulations to birds or mammals.

The Agency gets ecotoxicity test values ( measurement endpoints) used in the acute and chronic risk quotients from required studies. Examples of ecotoxicity values gathered from short term laboratory studies that assess acute effects are: ( 1) LC 50 ( fish and birds); ( 2) LD 50 ( birds and mammals); ( 3) EC 50 ( aquatic plants and aquatic invertebrates); and ( 4) EC 25 ( terrestrial plants). Examples of toxicity test effect levels drawn from the results of long term laboratory studies that assess chronic effects are: ( 1) LOAEL or LOAEC ( birds, fish, and aquatic invertebrates) and ( 2) NOAEL or NOAEC ( birds, fish and aquatic invertebrates). For birds, mammals, fish and aquatic invertebrates, the Agency uses the NOAEL or NOAEC as the ecotoxicity test value in assessing chronic effects, although the Agency may use other values when justified. Tabulated below are risk presumptions and the matching RQs and LOCs.

Risk quotients are index or reference values used to show potential ecological risk. There are limits with the use of risk quotients in assessing the risk to nontarget animals and plants. The likelihood of an adverse effect does not increase with the size of the risk quotient. ( Urban, 2000). An LOC defined as 1 ( see table below) provides the reference point for estimating the exposure to toxicity risk ( that is, risk quotient). Values at or above this reference point trigger risk concerns. A risk quotient value of 100 compared to a value of 50 does not suggest a greater risk or a risk that is more likely to occur. Both these values are above the reference point for risk of 1. The risk quotient value of 100 reflects an exposure level that is twice as high as the risk quotient value of 50. The " exposure" in the " RQ = Exposure/ Toxicity" ratio is twice has high for RQ of 100 as for the RQ of 50. Risk quotients are nonprobabilistic and have numerical and dichotomous results. The numerical result drawn from the calculation either exceeds a fixed LOC or does not exceed it. ( US EPA. June 30, 1995). 65 Table 1. Risk presumptions for terrestrial animals based on risk quotients ( RQ) and levels of concern ( LOC).

Risk Presumption RQ LOC Birds Acute Risk EEC1/ LC 50 or LD 50 / ft2 or LD 50 / day3 0.5 Acute Restricted Use EEC/ LC 50 or LD 50 / ft2 or LD 50 / day ( or LD 50 < 50 mg/ kg) 0.2 Acute Endangered Species EEC/ LC 50 or LD 50 / ft2 or LD 50 / day 0.1 Chronic Risk EEC/ NOAEC 1 Wild Mammals Acute Risk EEC/ LC 50 or LD 50 / ft2 or LD 50 / day 0.5 Acute Restricted Use EEC/ LC 50 or LD 50 / ft2 or LD 50 / day ( or LD 50 < 50 mg/ kg) 0.2 Acute Endangered Species EEC/ LC 50 or LD 50 / ft2 or LD 50 / day 0.1 Chronic Risk EEC/ NOAEC 1 1 abbreviation for Estimated Environmental Concentration ( ppm) on avian/ mammalian food items 2 mg/ ft2 3 mg of toxicant consumed/ day LD 50 * wt. of bird LD 50 * wt. of bird Table 2. Risk presumptions for aquatic animals based on risk quotients ( RQ) and levels of concern ( LOC).

Risk Presumption RQ LOC Acute Risk EEC1/ LC 50 or EC 50 0.5 Acute Restricted Use EEC/ LC 50 or EC 50 0.1 Acute Endangered Species EEC/ LC 50 or EC 50 0.05 Chronic Risk EEC/ NOAEC 1 1 EEC = ( ppm or ppb) in water Table 3. Risk presumptions for plants based on risk quotients ( RQ) and levels of concern ( LOC).

Risk Presumption RQ LOC Terrestrial and Semi Aquatic Plants Acute Risk EEC1/ EC 25 1 Acute Endangered Species EEC/ EC 05 or NOAEC 1 Aquatic Plants Acute Risk EEC2/ EC 50 1 Acute Endangered Species EEC/ EC 05 or NOAEC 1 1 EEC = lbs ai/ A 2 EEC = ( ppb/ ppm) in water b. Exposure and Risk to Terrestrial Animals i. Birds EFED is unable to assess the acute or chronic risk to birds because the toxicity of ETU to these organisms is unknown. EFED is requiring that studies to provide this toxicity information through this 66 document ( see appendices III and V).

ii. Mammals As identified in Appendix III, ETU is practically nontoxic ( mouse acute oral LD 50 = 2,300 mg/ kg) to mammals. Because of this, EFED expects ETU to present a low acute risk to mammals so EFED did not calculate RQs for acute exposure.

Tabulated below, in tables 4 and 4a, are the chronic mammalian risk quotients of ETU for multiple broadcast applications of nongranular mancozeb products. The EECs modeled for ETU assumes 1.6 percent conversion of mancozeb to ETU as an estimate of exposure. EFED also assumed a 35 day total foliar residue dissipation half life for ETU in predicting EECs. The RQs produced for ETU in this table are the RQs that EFED would expect from the use patterns for mancozeb. EFED could have created similar RQs based on the use patterns of the other two parent compounds for ETU, metiram and maneb. EFED chose not to perform more calculations for metiram and maneb, since further RQ calculations would be comparable confirming ETU's chronic risk to mammals. In addition, mancozeb, of the three EBDC fungicides, has the broadest use pattern ( most sites of application) and thus EFED expected mancozeb to provide a more comprehensive view of the chronic risks posed by ETU. ETU's RQs exceeded chronic LOCs for all mancozeb's uses. For small mammals ( 15 gram) feeding on short grass, the chronic RQs range from a high of 37.79 from mancozeb turf applications to 1.73 from mancozeb citrus applications. For medium sized mammals ( 35 gram) feeding on short grass, ETU's chronic RQ range from 26.25 for turf applications of mancozeb to 1.2 on citrus. For large mammals ( 1,000 gram) feeding on short grass, the RQs range from 5.97 on turf to 1.07 on bananas. There are no ETU chronic LOC exceedances to large mammals from mancozeb's use on potato & sugar beet, fennel, peanuts, forestry ( douglas fir), Christmas tree plantations, tobacco, cotton, asparagus, garlic & shallot, ornamentals, barley, etc., vegetables or citrus. EFED also calculated the RQs for granivore mammals. For mammalian granivores, no chronic LOC for ETU from mancozeb's uses was exceeded ( see Table 4a for details). ETU effects triggering this chronic risk were based on developmental defects of the brain ( that is, exencephaly, dilated ventricles, and hypoplastic cerebellum) in rats. 67 Table 4: Mammalian ( Herbivore/ Insectivore) Chronic Risk Quotients From ETU Exposure for Multiple Applications of Mancozeb Nongranular ( Broadcast) Using a NOAEL of 5 mg/ kg/ day for Mancozeb's Metabolite, ETU, based on developmental defects of the brain ( exencephaly, dilated ventricles, and hypoplastic cerebellum) in a study on labaratory rats ( Rattus norvegicus).

Maximum Application Rate Chronic RQ Maximum EEC ( mg/ kg) Maximum ( lbs ai/ A)/

Chronic RQ Forage & Chronic RQ EEC ( mg/ kg) Forage & EEC ( mg/ kg) % Body Body Number of Large Small Short Large Small Short Weight Weight Applications/ Site/

Insects 2,3 Insects 2,3 Grass 2,3 Insects 1 Insects 1 Grass1 Consumed ( grams) Interval Application Method/

0.72 6.48 11.52 4 34 61 95 15 4.8/ 4 Apples, Cranapple,

0.50 4.50 8.00 4 34 61 66 35 7 day interval Pear, & Quince 0.11 1.02 1.82 4 34 61 15 1000 ground & aerial 0.22 2.00 3.56 1 11 19 95 15 1.6/ 4 Asparagus 0.15 1.39 2.47 1 11 19 66 35 10 day interval ground & aerial 0.04 0.32 0.56 1 11 19 15 1000 0.42 3.81 6.78 2 20 36 95 15 2.4/ 10 Bananas & Plantain 0.29 2.65 4.71 2 20 36 66 35 14 day interval ground & aerial 0.07 0.60 1.07 2 20 36 15 1000 0.19 1.73 3.07 1 9 16 95 15 1.6/ 3 Barley, Oats, Rye,

0.13 1.20 2.13 1 9 16 66 35 7 day interval Triticale, & Wheat 0.03 0.27 0.48 1 9 16 15 1000 ground & aerial 0.11 0.97 1.73 1 5 9 95 15 0.9/ 3 a Citrus 0.07 0.67 1.20 1 5 9 66 35 7 day interval ground & aerial 0.02 0.15 0.27 1 5 9 15 1000 0.50 4.50 7.99 3 24 42 95 15 1.2/ 15 Corn ( unspecified)

0.35 3.12 5.55 3 24 42 66 35 4 day interval ( E. of Miss. River)

0.08 0.71 1.26 3 24 42 15 1000 ground & aerial 0.39 3.54 6.29 2 19 33 95 15 1.2/ 10 Corn ( unspecified)

0.27 2.46 4.37 2 19 33 66 35 4 day interval ( W. of Miss. River)

0.06 0.56 0.99 2 19 33 15 1000 ground & aerial 0.22 2.00 3.56 1 11 19 95 15 1.6/ 4 Cotton 0.15 1.39 2.47 1 11 19 66 35 10 day interval ground & aerial 0.04 0.32 0.56 1 11 19 15 1000 0.58 5.18 9.20 3 27 48 95 15 4.8/ 3 Cranberry 0.40 3.60 6.39 3 27 48 66 35 7 day interval ground & aerial 0.09 0.82 1.45 3 27 48 15 1000 68 Table 4: Mammalian ( Herbivore/ Insectivore) Chronic Risk Quotients From ETU Exposure for Multiple Applications of Mancozeb Nongranular ( Broadcast) Using a NOAEL of 5 mg/ kg/ day for Mancozeb's Metabolite, ETU, based on developmental defects of the brain ( exencephaly, dilated ventricles, and hypoplastic cerebellum) in a study on labaratory rats ( Rattus norvegicus).

Application Rate Chronic RQ EEC ( mg/ kg) ( lbs ai/ A)/

Chronic RQ Forage & Chronic RQ EEC ( mg/ kg) Forage & EEC ( mg/ kg) % Body Body Number of Large Small Short Large Small Short Weight Weight Applications/ Site/

Insects 2,3 Insects 2,3 Grass 2,3 Insects 1 Insects 1 Grass1 Consumed ( grams) Interval Application Method/

0.57 5.10 9.06 3 27 48 95 15 2.4/ 8 Cucumber 0.39 3.54 6.30 3 27 48 66 35 7 day interval ground & aerial 0.09 0.81 1.43 3 27 48 15 1000 0.38 3.40 6.04 2 18 32 95 15 1.6/ 8 Fennel 0.26 2.36 4.20 2 18 32 66 35 7 day interval ground & aerial 0.06 0.54 0.95 2 18 32 15 1000 0.64 5.73 10.19 3 30 54 95 15 3.2/ 6 Grapes 0.44 3.98 7.08 3 30 54 66 35 7 day interval ( E. of Rocky Mtns.)

0.10 0.90 1.61 3 30 54 15 1000 ground & aerial 0.24 2.16 3.84 1 11 20 95 15 2.0/ 3 Grapes 0.17 1.50 2.66 1 11 20 66 35 7 day interval ( W. of Rocky Mtns.)

0.04 0.34 0.61 1 11 20 15 1000 ground & aerial 0.57 5.10 9.06 3 27 48 95 15 2.4/ 8 Melons & Squash 0.39 3.54 6.30 3 27 48 66 35 7 day interval ground & aerial 0.09 0.81 1.43 3 27 48 15 1000 0.63 5.71 10.15 3 30 53 95 15 2.4/ 10 Onion, Garlic, & Shallot 0.44 3.96 7.05 3 30 53 66 35 7 day interval ground & aerial 0.10 0.90 1.60 3 30 53 15 1000 0.97 8.71 15.48 5 46 81 95 15 4.0/ 7 Papaya 0.67 6.05 10.75 5 46 81 66 35 5 day interval ground & aerial 0.15 1.37 2.44 5 46 81 15 1000 0.38 3.40 6.04 2 18 32 95 15 1.6/ 8 Peanuts 0.26 2.36 4.20 2 18 32 66 35 7 day interval ground & aerial 0.06 0.54 0.95 2 18 32 15 1000 69 Table 4: Mammalian ( Herbivore/ Insectivore) Chronic Risk Quotients From ETU Exposure for Multiple Applications of Mancozeb Nongranular ( Broadcast) Using a NOAEL of 5 mg/ kg/ day for Mancozeb's Metabolite, ETU, based on developmental defects of the brain ( exencephaly, dilated ventricles, and hypoplastic cerebellum) in a study on labaratory rats ( Rattus norvegicus ).

Application Rate Chronic RQ EEC ( mg/ kg) ( lbs ai/ A)/

Chronic RQ Forage & Chronic RQ EEC ( mg/ kg) Forage & EEC ( mg/ kg) % Body Body Number of Large Small Short Large Small Short Weight Weight Applications/ Site/

Insects 2,3 Insects 2,3 Grass 2,3 Insects 1 Insects 1 Grass1 Consumed ( grams) Interval Application Method/

0.39 3.48 6.19 2 18 33 95 15 1.6/ 7 Potato & Sugar Beet 0.27 2.42 4.30 2 18 33 66 35 5 day interval ground & aerial 0.06 0.55 0.98 2 18 33 15 1000 0.25 2.24 3.98 1 12 21 95 15 2.0/ 3 a Tobacco 0.17 1.55 2.76 1 12 21 66 35 5 day interval ground & aerial 0.04 0.35 0.63 1 12 21 15 1000 0.53 4.73 8.40 3 25 44 95 15 2.4/ 7 Tomato 0.36 3.28 5.84 3 25 44 66 35 7 day interval ground & aerial 0.08 0.75 1.33 3 25 44 15 1000 0.18 1.62 2.88 1 9 15 95 15 1.5/ 3 a Vegetablesb 0.12 1.12 2.00 1 9 15 66 35 7 day interval ground & aerial 0.03 0.26 0.45 1 9 15 15 1000 0.34 3.06 5.45 2 16 29 95 15 3.2/ 3 a Forestry ( Douglas Fir)

0.24 2.13 3.78 2 16 29 66 35 14 day interval ground & aerial 0.05 0.48 0.86 2 16 29 15 1000 0.34 3.06 5.45 2 16 29 95 15 3.2/ 3 a Ornamental Trees c 0.24 2.13 3.78 2 16 29 66 35 14 day interval ground & aerial 0.05 0.48 0.86 2 16 29 15 1000 0.19 1.73 3.07 1 9 16 95 15 1.6/ 3 a Ornamentals d 0.13 1.20 2.13 1 9 16 66 35 7 day interval ground & aerial 0.03 0.27 0.48 1 9 16 15 1000 2.22 19.96 35.48 12 105 187 95 15 13.9/ 5 Ornamentals 1.54 13.86 24.65 12 105 187 66 35 10 day interval ( pachysandra groundcover)

0.35 3.15 5.60 12 105 187 15 1000 ground 2.16 19.47 34.61 11 102 182 95 15 17.4/ 3 a Turf ( golf course)

1.50 13.52 24.04 11 102 182 66 35 5 day interval ground 0.34 3.07 5.46 11 102 182 15 1000 2.36 21.26 37.79 12 112 199 95 15 19.0/ 3 a Turf e 1.64 14.77 26.25 12 112 199 66 35 5 day interval ground & aerial 0.37 3.36 5.97 12 112 199 15 1000 1 Assumes degradation using FATE version 5.0 program with an ETU total foliar residue half life of 35 days and mancozeb to ETU conversion rate of 1.6%.

2 RQ = EEC ( mg/ kg)/[ NOAEL ( mg/ kg bw/ day)/ %( decimal) Body Weight Consumed ( bw/ day)] 3 RQ greater or equal to 1.0 exceeds chronic risk LOCs.

a Maximum number of applications/ year or crop cycle not specified ( assumed 3 applications).

b Beets ( unspecified), Broccoli, Brussel sprouts, Cabbage, Carrots, Cauliflower, Chard ( Swiss),

Collards, Coriander, Dill, Endive, Kale, Kohlrabi, Leeks, Lettuce, Mustard, Mustard Cabbage,

Parsley, Parsnip, Radish, Rape, Roquette ( Arrugula), Rutabaga, Spinach, & Turnip c Christmas Tree Plantations d Trees, Herbaceous Plants, Non Flowering Plants, & Woody Shrubs and Vines e Commercial/ Industrial, Sod Farm & Residential 70 Table 4a: Mammalian ( Granivore) Chronic Risk Quotients From ETU Exposure for Multiple Applications of Mancozeb Nongranular ( Broadcast) Using a NOAEL of 5 mg/ kg/ day for Mancozeb's Metabolite, ETU, based on developmental defects of the brain ( exencephaly, dilated ventricles, and hypoplastic cerebellum) in a study on labaratory rats ( Rattus norvegicus).

Application Rate ( lbs ai/ A)/

Maximum % Body Body Number of Chronic RQ EEC ( mg/ kg) Weight Weight Applications/ Site/

Seeds 2,3 Seeds1 Consumed ( grams) Interval Application Method/

0.16 4 21 15 4.8/ 4 Apples, Cranapple,

0.11 4 15 35 7 day interval Pear, & Quince 0.02 4 3 1000 ground & aerial 0.05 1 21 15 1.6/ 4 Asparagus 0.04 1 15 35 10 day interval ground & aerial 0.01 1 3 1000 0.09 2 21 15 2.4/ 10 Bananas & Plantain 0.07 2 15 35 14 day interval ground & aerial 0.01 2 3 1000 0.04 1 21 15 1.6/ 3 Barley, Oats, Rye,

0.03 1 15 35 7 day interval Triticale, & Wheat 0.01 1 3 1000 ground & aerial 0.02 1 21 15 0.9/ 3 a Citrus 0.02 1 15 35 7 day interval ground & aerial 0.00 1 3 1000 0.11 3 21 15 1.2/ 15 Corn ( unspecified)

0.08 3 15 35 4 day interval ( E. of Miss. River)

0.02 3 3 1000 ground & aerial 0.09 2 21 15 1.2/ 10 Corn ( unspecified)

0.06 2 15 35 4 day interval ( W. of Miss. River)

0.01 2 3 1000 ground & aerial 0.05 1 21 15 1.6/ 4 Cotton 0.04 1 15 35 10 day interval ground & aerial 0.01 1 3 1000 0.13 3 21 15 4.8/ 3 Cranberry 0.09 3 15 35 7 day interval ground & aerial 0.02 3 3 1000 71 Table 4a: Mammalian ( Granivore) Chronic Risk Quotients From ETU Exposure for Multiple Applications of Mancozeb Nongranular ( Broadcast) Using a NOAEL of 5 mg/ kg/ day for Mancozeb's Metabolite, ETU, based on developmental defects of the brain ( exencephaly, dilated ventricles, and hypoplastic cerebellum) in a study on labaratory rats ( Rattus norvegicus).

Application Rate ( lbs ai/ A)/

% Body Body Number of Chronic RQ EEC ( mg/ kg) Weight Weight Applications/ Site/

Seeds 2,3 Seeds1 Consumed ( grams) Interval Application Method/

0.13 3 21 15 2.4/ 8 Cucumber 0.09 3 15 35 7 day interval ground & aerial 0.02 3 3 1000 0.08 2 21 15 1.6/ 8 Fennel 0.06 2 15 35 7 day interval ground & aerial 0.01 2 3 1000 0.14 3 21 15 3.2/ 6 Grapes 0.10 3 15 35 7 day interval ( E. of Rocky Mtns.)

0.02 3 3 1000 ground & aerial 0.05 1 21 15 2.0/ 3 Grapes 0.04 1 15 35 7 day interval ( W. of Rocky Mtns.)

0.01 1 3 1000 ground & aerial 0.13 3 21 15 2.4/ 8 Melons & Squash 0.09 3 15 35 7 day interval ground & aerial 0.02 3 3 1000 0.14 3 21 15 2.4/ 10 Onion, Garlic, & Shallot 0.10 3 15 35 7 day interval ground & aerial 0.02 3 3 1000 0.21 5 21 15 4.0/ 7 Papaya 0.15 5 15 35 5 day interval ground & aerial 0.03 5 3 1000 0.08 2 21 15 1.6/ 8 Peanuts 0.06 2 15 35 7 day interval ground & aerial 0.01 2 3 1000 72 Table 4a: Mammalian ( Granivore) Chronic Risk Quotients From ETU Exposure for Multiple Applications of Mancozeb Nongranular ( Broadcast) Using a NOAEL of 5 mg/ kg/ day for Mancozeb's Metabolite, ETU, based on developmental defects of the brain ( exencephaly, dilated ventricles, and hypoplastic cerebellum) in a study on labaratory rats ( Rattus norvegicus ).

Application Rate ( lbs ai/ A)/

% Body Body Number of Chronic RQ EEC ( mg/ kg) Weight Weight Applications/ Site/

Seeds 2,3 Seeds1 Consumed ( grams) Interval Application Method/

0.09 2 21 15 1.6/ 7 Potato & Sugar Beet 0.06 2 15 35 5 day interval ground & aerial 0.01 2 3 1000 0.05 1 21 15 2.0/ 3a Tobacco 0.04 1 15 35 5 day interval ground & aerial 0.01 1 3 1000 0.12 3 21 15 2.4/ 7 Tomato 0.08 3 15 35 7 day interval ground & aerial 0.02 3 3 1000 0.04 1 21 15 1.5/ 3a Vegetablesb 0.03 1 15 35 7 day interval ground & aerial 0.01 1 3 1000 0.08 2 21 15 3.2/ 3a Forestry ( Douglas Fir)

0.05 2 15 35 14 day interval ground & aerial 0.01 2 3 1000 0.08 2 21 15 3.2/ 3a Ornamental Treesc 0.05 2 15 35 14 day interval ground & aerial 0.01 2 3 1000 0.04 1 21 15 1.6/ 3a Ornamentalsd 0.03 1 15 35 7 day interval ground & aerial 0.01 1 3 1000 0.49 12 21 15 13.9/ 5 Ornamentals 0.35 12 15 35 10 day interval ( pachysandra groundcover)

0.07 12 3 1000 ground 0.48 11 21 15 17.4/ 3a Turf ( golf course)

0.34 11 15 35 5 day interval ground 0.07 11 3 1000 0.52 12 21 15 19.0/ 3a Turfe 0.37 12 15 35 5 day interval ground & aerial 0.07 12 3 1000 1 Assumes degradation using FATE version 5.0 program with an ETU total foliar residue half life of 35 days and mancozeb to ETU conversion rate of 1.6%

2 RQ = EEC ( mg/ kg)/[ NOAEL ( mg/ kg bw/ day)/ %( decimal) Body Weight Consumed ( bw/ day)] 3 RQ greater or equal to 1.0 exceeds chronic risk LOCs.

a Maximum number of applications/ year or crop cycle not specified ( assumed 3 applications).

b Beets ( unspecified), Broccoli, Brussel sprouts, Cabbage, Carrots, Cauliflower, Chard ( Swiss),

Collards, Coriander, Dill, Endive, Kale, Kohlrabi, Leeks, Lettuce, Mustard, Mustard Cabbage,

Parsley, Parsnip, Radish, Rape, Roquette ( Arrugula), Rutabaga, Spinach, & Turnip c Christmas Tree Plantations d Trees, Herbaceous Plants, Non Flowering Plants, & Woody Shrubs and Vines e Commercial/ Industrial, Sod Farm & Residential 73 c. Aquatic Organisms i. Review The industry EBDC task force collected targeted, surface water recording data ( MRID No. 46145401). In two years of sampling, at sites selected to be the most vulnerable nationally, monitoring data failed to showed concentration values above the method detection limit for ETU ( that is, 0.1 ppb). The industry collected samples only every two weeks during the EBDC use season and it could be this sampling missed daily concentration values above the detection limit. However, In two years of sampling, at sites selected to be the most vulnerable nationally, monitoring data failed to showed concentration values above the method detection limit for ETU ( that is, 0.1 ppb). EFED based the surface water exposure EECs for ETU on the results of screening models to provide the preliminary EEC estimates. EFED calculated surface water concentrations of ETU using the Pesticide Root Zone Model version 3.1.2 beta ( Carsel and others, 1997) and Exposure Analysis Modeling System version 2.98.04 ( Burns, 1997) ( PRZM EXAMS) for Tier II estimates ( see section V. Water Resource Assessment, for detailed explanation).. EFED used the peak EECs to assess the acute risks to aquatic organisms from multiple applications. 74 Table 5: ETU Acute Risk Quotients for Freshwater Fish Based On a Rainbow Trout ( Oncorhynchus mykiss) LC50 of > 502 ppm. Application Rate ( lbs ai/ A)/ Number of Acute RQ Applications/ Site/ ( Peak EEC/ LC50) 2 EEC Peak ( ppb) 1 Interval Application Method/

2.2E 05 11.2 4.8/ 4 Apples 7 day interval ground & aerial 1.7E 05 8.6 2.4/ 10 Onion 7 day interval ground & aerial 2.5E 05 12.3 1.6/ 6 Peppers 7 day interval ground & aerial 8.6E 06 4.3 1.6/ 10 Potatoes 5 day interval ground & aerial 2.2E 05 11.0 1.2/ 15 Sweet Corn 4 day interval ground & aerial 2.2E 05 10.9 2.4/ 7 Tomato 7 day interval ground & aerial 6.4E 05 31.8 17.4/ 3 Turf 7 day interval ground & aerial 4.4E 06 2.2 1.6/ 3 Wheat 7 day interval ground & aerial 1 Based on PRZM version 3.12/ EXAMS version 2.97.5 modeling. Application rates in this table are parent EBDC label rates. Rates in all ETU simulations are pre multiplied by the molar conversion rate of 0.385 2 RQ greater or equal to 0.5 exceeds acute high risk, acute restricted use and acute endangered species LOCs.

RQ greater or equal to 0.1 exceeds acute restricted use and acute endangered species LOCs.

RQ greater or equal to 0.05 exceeds acute endangered species LOCs. ii. Freshwater Fish Tabulated below, in Table 5, are ETU's acute risk quotients for freshwater fish. The results show that no acute risk exceed LOCs. 75 Table 6: ETU Acute Risk Quotients for Freshwater Invertebrates Based On a Waterflea ( Daphnia magna ) LC50 of 26.9 ppm. Application Rate ( lbs ai/ A)/ Number of Acute RQ Applications/ Site/ ( Peak EEC/ LC50) 2 EEC Peak ( ppb) 1 Interval Application Method/

4.2E 04 11.2 4.8/ 4 Apples 7 day interval ground & aerial 3.2E 04 8.6 2.4/ 10 Onion 7 day interval ground & aerial 4.6E 04 12.3 1.6/ 6 Peppers 7 day interval ground & aerial 1.6E 04 4.3 1.6/ 10 Potatoes 5 day interval ground & aerial 4.1E 04 11.0 1.2/ 15 Sweet Corn 4 day interval ground & aerial 4.1E 04 10.9 2.4/ 7 Tomato 7 day interval ground & aerial 1.2E 03 31.8 17.4/ 3 Turf 7 day interval ground & aerial 8.2E 05 2.2 1.6/ 3 Wheat 7 day interval ground & aerial 1 Based on PRZM version 3.12/ EXAMS version 2.97.5 modeling. Application rates in this table are parent EBDC label rates. Rates in all ETU simulations are pre multiplied by the molar conversion rate of 0.385 2 RQ greater or equal to 0.5 exceeds acute high risk, acute restricted use and acute endangered species LOCs.

RQ greater or equal to 0.1 exceeds acute restricted use and acute endangered species LOCs.

RQ greater or equal to 0.05 exceeds acute endangered species LOCs. iii. Freshwater Invertebrates Tabulated in Table 6, are ETU's acute risk quotients for freshwater invertebrates. The results point to no acute risk LOCs exceedances. 76 Table 7: ETU Acute Risk Quotients for Aquatic Non Vascular Plants Based Upon a Freshwater Green Algae ( Pseudokirchneriella subcapitata ) EC50 of 23 ppm Application Rate ( lbs ai/ A)/

Number of Acute RQ Applications/ Site/

( Peak EEC/ LC50) 2 EEC Peak ( ppb) 1 Interval Application Method/

4.9E 04 11.2 4.8/ 4 Apples 7 day interval ground & aerial 3.7E 04 8.6 2.4/ 10 Onion 7 day interval ground & aerial 5.3E 04 12.3 1.6/ 6 Peppers 7 day interval ground & aerial 1.9E 04 4.3 1.6/ 10 Potatoes 5 day interval ground & aerial 4.8E 04 11.0 1.2/ 15 Sweet Corn 4 day interval ground & aerial 4.7E 04 10.9 2.4/ 7 Tomato 7 day interval ground & aerial 1.4E 03 31.8 17.4/ 3 Turf 7 day interval ground & aerial 9.6E 05 2.2 1.6/ 3 Wheat 7 day interval ground & aerial 1 Based on PRZM version 3.12/ EXAMS version 2.97.5 modeling. Application rates in this table are parent EBDC label rates. Rates in all ETU simulations are pre multiplied by the molar conversion rate of 0.385 2 RQ greater or equal to 1.0 exceeds acute risk LOCs. iv. Exposure and Risk to Nontarget Plants: Aquatic Plants Exposure to nontarget aquatic plants may occur through runoff or spray drift from bordering treated sites. EFED uses the surrogate species, duckweed ( Lemna gibba) to make a risk determination for aquatic vascular plants. EFED performs nonvascular, aquatic plant acute risk assessments using either algae or a diatom, whichever is the most sensitive species. There are no known nonvascular plant species on the endangered species list. EFED models runoff and drift exposure from PRZMEXAMS EFED calculates risk quotient by dividing ETU's peak concentration in water by the plant EC 50 value.

Table 7 shows the acute risk quotients for freshwater, nonvascular green alga ( Pseudokirchneriella subcapitata) plants. The results show no acute risk LOCs exceedances. 77 d. Endangered Species Based on available screening level information there is a potential concern for chronic ETU effects on listed mammals should exposure actually occur. Chronic ETU RQs exceed LOCs for endangered and threatened species of mammals. The Agency does not currently have data on which to evaluate the toxicity of ETU to endangered or threatened birds, estuarine/ marine fish, or aquatic vascular plants. Thus, risks to endangered or threatened species of birds, estuarine/ marine fish, or aquatic vascular plants from ETU exposure is uncertain. EFED is requiring the data to assess the potential risk to endangered or threatened species of birds, estuarine/ marine fish, or aquatic vascular plants through this document. EFED is reserving the terrestrial plant ETU data needs until EFED receives and completes review of the parent EBDC's toxicity to terrestrial plants.

e. Ecological Incidents The USEPA Ecological Incident Information System ( EIIS) ( see Appendix VI for description and background), did not provide any ETU incident reports. 78 APPENDIX V: US EPA Ecological Incident Information System The Office of Pesticide Programs ( OPP) has tracked incidents reports, given to EPA since about 1994, by assigning identification number in an Incident Data System ( IDS) and microfiching the reports. The Environmental Fate and Effects Division ( EFED) then enters the ecological related incident reports into a second database, the Ecological Incident Information System ( EIIS). This second database has some 85 fields for potential data entry. EFED has also made an effort to enter information into EIIS on incident reports received before establishment of current databases. Although EFED has added many of these reports, EIIS does not yet provide a listing of all incident reports received by EPA. OPP does not receive incident reports in a consistent format. For example, states and various labs usually have their own report formats. The incidents reports may involve multiple incidents involving multiple chemicals in one report, and may report on only part of an incident investigation ( for example, residues). EFED has made some progress in recent years, both in getting incident reports sent and entered. However, there has never been enough staff time and effort assigned to recording incidents. For example, the staff time and effort assigned to tracking and reviewing laboratory toxicity studies are greater than those assigned to tracking incidents.

EFED classifies EIIS entered incidents into one of several certainty levels: highly probable, probable, possible, unlikely, or unrelated. In brief, " highly probable" incidents usually need carcass residues, show large cholinesterase inhibition ( for chemicals such as organophosphates that depress brain and blood cholinesterase), or clear circumstances about the exposure. " Probable" incidents include those where residues were not available or circumstances were less clear than for " highly probable." " Possible" incidents include those where multiple chemicals may have been involved and it is not clear what the contribution was of a given chemical. OPP use the " unlikely" category, for example, where a given chemical is almost nontoxic to the category of organism killed or the chemical was tested for but not detected in samples. " Unrelated" incidents are those that OPP confirms as not pesticiderelated

EFED also classes EIIS entered incidents as use or misuse. Unless specifically confirmed by a state or federal agency to be misuse, or there was clear misuse such as intentional baiting to kill wildlife, EFED would not typically consider incidents to be misuse. For example, data entry personnel often do not have a copy of the specific label used in a given application, and would not usually be able to detect various label specific violations.

EFED believes the number pesticide related incidents reported in EIIS, while large, are a small fraction of pesticide incidents. EIIS entered incidents requires that mortality incidents be seen, reported, examined, and have investigation reports sent to EPA. Incidents often are not seen, because of scavenger removal of carcasses, decay in a field, or simply because carcasses may be hard to see on many sites. Poisoned wildlife may also move off site to less visible areas before dying. Incidents often are not seen because few people are systematically looking. Finders, seeing incidents, may not report incidents to suitable authorities to examine the incident. The finder may not know that it is important to report incidents or may not know who to contact. He or she may not feel they have the time or wish to make a telephone call, may hesitate to call because of their own involvement in the kill, or the call may be long distance which may discourage the caller. Incidents reported may not 79 get examined if time or people are limited or may not get examined thoroughly, with residue and cholinesterase analyzes, for example. Also, if kills are not reported and examined at once, there will be little chance of documenting the cause, since tissues and residues may decay quickly. States often do not send reports of examined incidents to EPA, since reporting by states is voluntary and some investigators may believe that they don't have the time or people to send incident reports to EPA. ( Felkel. 2000) APPENDIX VI. HED Memorandum on Surface/ Ground water EDWCs U. S. ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, DC 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES DP Barcode: D290057 Date: August 26, 2004 MEMORANDUM SUBJECT: Revision No. 2: Estimated Drinking Water Concentrations of Ethylenebisdithiocarbamate ( EBDC) Degradate Ethylenethiourea ( ETU) for the Use in Human Health Risk Assessment FROM: Ronald Parker, Senior Environmental Engineer, Ph. D. Environmental Risk Branch V Environmental Fate and Effects Division ( 7507C)

Mohammed Ruhman, Agronomist, Ph. D. Environmental Risk Branch V Environmental Fate and Effects Division ( 7507C)

THROUGH: Mah T. Shamim, Ph. D., Chief Environmental Risk Branch V Environmental Fate and Effects Division ( 7507C)

TO: Anthony Britten Tawanda Spears Chemical Review Manager Registration Division AND Christina Swartz Health Effects Division Summary This is a revised memo presenting the Estimated Drinking Water Concentrations ( EDWCs) for the EBDC degradate ETU for use in an FQPA human health risk assessment. The EBDC fungicides, Metiram, Maneb and Mancozeb are very short lived in soil and in water and would not themselves be expected to remain in surface water long enough to reach a location that would supply water for human consumption whether from surface or groundwater. 81 Ethylenethiourea ( ETU) is a common metabolite of all of the EBDC fungicides and may reach both surface and groundwater under some conditions. This assessment addresses exposure to ETU only. The chronic EDWC for surface water is 0.1 ppb and is based on a monitoring study conducted by the EBDC Task Force. A range of acute EDWCs is established with a lower limit of 0.1 ppb ( based on monitoring) and an upper limit of 25.2 ppb ( based on environmental fate and transport simulation modeling using the linked EPA PRZM and EXAMS models). The ground water EDWC is 0.21 ppb ( based on a targeted monitoring study).

The currently approved version of PRZM is only capable of simulating pesticide metabolites through use of simplifying assumptions. The level of uncertainty in the estimated ETU concentration values is therefore relatively high. The targeted surface water monitoring study provides a lower bound for the drinking water exposure estimate. No concentration values above the ETU limit of detection of 0.1 ppb were found in this study. However, acute peak values could have been missed as a result of the 14 day sampling intervals.

The PRZM/ EXAMS simulation modeling was performed for 22 crop scenarios. The use patterns for all EBDCs were considered and the highest application rate/ lowest application intervals were chosen for modeling. Results indicate that the highest one in ten year acute surface water EDWC was found to be 25.2 ppb from the Florida pepper scenario with the lowest value being 4.5 ppb from the North Dakota wheat scenario. The highest chronic concentration value was 1.9 ppb from the California onion scenario with the lowest value being 0.2 ppb from the North Dakota wheat scenario. All these acute and chronic values include adjustment by the national maximum default percent cropped area ( PCA) value of 0.87. Use of the maximum regional PCA values resulted in a reduction of acute/ chronic EDWCs and in changes in scenarios giving the lowest/ highest values. In this case, the highest one in ten year acute surface water EDWCs was 13.9 ppb from California onions scenario with the lowest being 1.4 ppb from Maine potatoes scenario. Both the national and the regional PCA values represent the maximum area planted in any crop. The calculation assumes, not models, very rapid degradation of the parent pesticide to ETU using the maximum observed conversion of parent to ETU in the aerobic soil systems of 9.6% and 23.6% in the water/ sediment systems.

Targeted ETU monitoring study showed no surface water concentrations above the detection limit of 0.1 ppb in samples taken pre and post treatment at vulnerable use sites at community drinking intakes in several states. Samples were take every 14 days during the application season for two years. While such sampling could have missed an acute peak value, the Agency believes that it did demonstrate that long term average chronic values would not exceed the detection limit.

For the purposes of this assessment, the range of acute EDWC values for surface water at the national level is expected to be between 0.1 ppb ( the detection limit) and 25.2 ppb ( the highest peak value from modeling after adjustment by the 0.87 national PCA). The highest value in this national level range can be reduced to 13.9 ppb ( the highest peak value from modeling after adjustment by the 0.56 California PCA). Both the chronic/ non cancer and the chronic/ cancer values are set conservatively at the 0.1 ppb detection limit. The groundwater EDWC concentration is 0.21 ppb and is derived from a community water system intake concentration measured during the targeted 82 monitoring study conducted by the EBDC Task Force from 2001 to 2003. In this respect, it is noted that ETU was not detected in any of the treated community drinking water in any of the sampled 84 sites even when it was detected in the raw water. The registrant claims that the absence of ETU in potable water from community water supplies is related to its rapid degradation resulting from aeration and chemical treatment ( i. e. chlorination). Home filters containing stages for water softening and particulate removal were reported to be ineffective at removing ETU Both these surface and groundwater values represent upper bound conservative estimates of the total ETU residual concentrations that might be found in drinking water derived from either surface water and groundwater sources due to the use of the EBDC fungicides.

Estimating Drinking Water Exposure from Surface Water Sources i. Combined Monitoring/ Modeling Approach A monitoring program was conducted by the EBDC Task Force from 2001 2003. In this program, raw and associated treated surface water were sampled every two weeks during the three months historical EBDC application season and quarterly for the remaining three quarters of each year for a period of two years ( 18 sampling events). A total of 22 sites were chosen to represent vulnerable and high historic EBDC use sites in the states of Maine ( 5 sites/ potatoes), New York ( 5 sites/ apples), Michigan ( total= 6 sites: 3 sites/ apples and 3 sites/ mixed grapes/ apples & nursery plants), Minnesota ( 2 sites/ potatoes), and Washington ( 4 sites/ apples). The results from this targeted monitoring program were used to assign the chronic and the lower limit of the acute EDWCs for drinking water from surface water. Samples were take every 14 days during the application season and acute values may have been missed. Therefore, a range of acute EDWCs is established with a lower limit based on monitoring and an upper limit based on environmental fate and transport simulation modeling using the linked EPA PRZM and EXAMS models. The Agency therefore used a combined approach to exposure assessment based on both targeted surface water monitoring and computer simulation to bracket the expected acute exposure level.

1. Targeted monitoring component Targeted surface water monitoring data was collected by the industry EBDC Task Force. In two years of sampling at sites selected to be the most vulnerable nationally, no concentration values were measured above the method detection limit for ETU of 0.1 ppb. EFED used GIS ( Attachment 1) to confirm relevance of surface/ groundwater sites to EBDCs use patterns, vulnerability and spatial distribution of the national drinking water intakes. Samples were collected only every two weeks during the usage season and it is possible that daily concentration values above the detection limit may have been missed. The agency does believe, however, that the sampling confirms that long term average chronic values above the detection limit will not occur.

The Agency has been unable to locate other surface water monitoring data for the EBDC fungicides or for ETU. These chemicals were not included in the US Geological Survey NAWQA sampling program because the test methods are incompatible with the methods used by that program. NAWQA measurements are frequently the best national source of pesticide monitoring data. The USGS is currently planning to begin method development and limited EBDC/ ETU monitoring in late 83 2004.

2. Modeling Component The monitoring based chronic EDWC of 0.1 ppb may represent the low limit of an acute range of values. Higher acute values can not be ruled out because monitoring was based on a 14 day sampling interval. Therefore, tier II drinking water estimates for ETU in surface water were calculated using the linked USEPA PRZM and EXAMS simulation models. Modeling results were first used to: ( 1) Assign a high limit to the acute EDWC range;

( 2) Compare chronic values obtained from modeling to the 0.1 ppb value assigned based on monitoring; and ( 3) Compare acute/ chronic values obtained for monitored areas to other areas of the country where surface water monitoring was not conducted in order to characterize the relevance of EDWC values obtained from monitoring 22 surface water sites for use at the national level.

Modeling Inputs This calculation assumes very rapid and complete degradation of the parent pesticide to ETU. ETU rate was not based on the molar conversion of 38.5% but rather on the maximum conversion rate of 9.6% observed in the laboratory aerobic soil studies for parent entering the soil system upon application and 23.6% for amounts entering the aquatic system by drift. These conversion rates were arrived at as a result of examination of fate and transport data of parent EBDCs which indicate that ETU is their major transformation product resulting from abiotic and biotic degradation processes in both field and laboratory studies. Reported laboratory data on degradation of EBDCs and the maximum ETU produced are summarized in Table 1.

Table 1. Maximum ETU produced in fate studies for parent EBDCs.

Type of Study Parent EBDCs Used as a Test Substance ( Number of Studies) Maximum ETU Formed As % Parent Equivalent As % ETU*

Aqueous Hydrolysis Maneb ( 1); Metiram ( 1) 93.0% 35.8%

Aero/ Anaerobic Aquatic Metiram ( 2); Maneb ( 1) 61.4% 23.6%

Aerobic Soil Metiram ( 4); Mancozeb ( 3); Maneb ( 3) 24.8% 09.6%

* % ETU= % Parent Equivalent multiplied by Molar ratio of ETU to Parent ( 38.5%). For example the maximum for hydrolysis studies= 93% x 0.385 = 35.8%.

Examination of data indicate that the maximum observed conversion of parent to ETU is expected to be the highest in water systems ( 35.8%) followed by water/ sediment systems ( 23.6%) and the lowest in aerobic soil systems ( 9.6%). Although these values represent the maximum found in the laboratory, higher or lower conversion rates may occur in the natural environment depending on the characteristics of the systems ( e. g. availability of moisture and biological activity). This is considered as an uncertainty along with the assumption that conversion to ETU occurs at application. In this respect, it is noted that the maximum ETU attained in the natural environment is a result of two major 21 This value is calculated as follows: Parent rate ( kg/ ha)= 5.38 arrived at by multiplying the parent rate of 4.8 ( lb/ a) by 1.121 ETU rate ( kg/ ha)= 0.52 arrived at by multiplying the parent rate of 5.38 ( kg/ ha) by 0.096 84 processes formation and degradation. This maximum is expected to occur shortly after the parent reaches the aquatic system by drift and much longer after foliar applied parent reaches the soil system.

In assigning the value for ETU application rate for modeling, EFED used the parent/ ETU conversion value of 9.6% for ETU expected to form ( from applied parent) in the soil system. This value ( equal to 0.52 kg a. i./ ha for apples21) was assigned to be the parent equivalent ETU rate. PRZM/ EXAMS will use this value to calculate drift by multiplying 0.52 by 0.16 ( 16% drift). This drift value is accurate only for the soil system and needs to be corrected for the aquatic system. Therefore, a correction factor of 2.458 was used and was affected by changing the drift from 0.16 ( the default value) to 0.393. Changing the drift fraction by the stated factor will result in an exact account for the observed 23.6% parent/ ETU conversion expected to form ( from parent drift) in aquatic systems.

Other inputs used for modeling are the fate and transport parameters determined for the EBDC metabolite/ degradate ETU. As shown in Table 2, ETU has an aerobic soil half life of about 3 days; in the absence of data, the aquatic aerobic metabolism half life was assumed to be about 6 days, or double the soil half life. The measured anaerobic aquatic metabolism half life, however, is substantially longer ( 149 days) possibly leading to the periodic detections in groundwater. It is highly soluble in water ( 20,000 ppm); highly vulnerable to indirect photolysis ( half life= 1 day), and moderately mobile ( 288 L/ kg). It also has a relatively high vapor pressure but high solubility reduces the possibility of losses from surface water due to volatilization.

Table 2. PRZM/ EXAMS Input Parameters for ETU.

Input Parameter Value Reference Molecular Weight ( grams) 102.2 Product chemistry submission Vapor Pressure ( torr) 9.728e 1 Registrant data Aerobic Soil Metabolism Half life ( days) 3.14 Upper confidence bound on the mean for three soils ( MRID 452251 01)

Bacterial Bio lysis in the water column ( days) ( Aerobic Aquatic metabolism half life) 6.28 Aerobic soil t ½ x2: No aerobic aquatic metabolism study/ No significant hydrolysis ( Guidance) 1 Bacterial Bio lysis in benthic sediment ( days) ( Anaerobic Aquatic metabolism half life) 447 Only one value is available= 149 days ( MRID 001633 35); use 149x3= 447 days ( Guidance) 1 Application Rate Varies by crop and calculated from parent rate as described above. Refer to Attachment 2 for a complete list of application rates/ dates used in modeling Application Method Aerial Product Label Depth of Incorporation ( inches) 0 Product Label National Percent Crop Area " PCA" ( fraction) 0.87 ( Guidance) 1 Input Parameter Value Reference 85 Spray Drift ( fraction) 0.393 This value is increased from the default value of 0.16 by a factor of 2.458 2. This was necessary to account for the difference in maximum conversion of ( parent to ETU) between the soil system ( 9.6%) and the aquatic system ( 23.6%)

Solubility ( mg/ L or ppm) 20,000 Product chemistry submission Koc ( L Kg 1) 288 Average for ten soils ( MRIDs 002588 96& 000971 58)

pH 7 Hydrolysis Half life ( days) Stable MRID 404661 03 Photolysis Half life( days) 1 This is the indirect photolysis half life reported for ETU; ETU is stable to direct photolysis ( MRID 404661 02)

1 Guidance for Chemistry and Management Practice Input Parameters For Use in Modeling the Environmental Fate and Transport of Pesticides, Version 2/ November 7, 2000.

2 This 2.458 correction factor was arrived at by dividing 23.6% ( conversion of parent to ETU in aquatic systems) by 9.6% ( conversion of parent to ETU in the soil systems which was used as the ETU application rate).

Modeling Outputs The PRZM/ EXAMS simulation modeling was performed for 22 crop scenarios to cover the extensive use patterns for all EBDCS. A Tier II EDWC for a particular crop or use is based on a single index reservoir site that represents a high exposure scenario for use on the crop. The scenarios are indexed to a vulnerable former drinking water reservoir located in Shipman, Illinois. Weather and agricultural practices are simulated at the site for 30 years to estimate the probability of exceeding a given concentration ( maximum concentration or average concentration) in a single year. Maximum EDWCs are calculated so that there is a 10% probability that the maximum concentration in a given year will exceed the EDWC at the site. Based on variability of weather, this can also be expressed as an expectation that water concentrations will exceed EDWCs once every 10 years. The results for all model runs are summarized below and background on the model along with complete results, additional inputs and sample outputs are attached for reference ( Attachment 2).

Table 3 summarizes results obtained for the highest peak values after adjustment by the national PCA of 0.87 and the regional PCA of 0.56 ( California). 86 Table 3. PRZM/ EXAMS highest peak values for the EDWCs of ETU from surface water.

Crop Scenario PCA Rates in kg/ ha ( Number of applications) EDWC ( ppb)

Parent ETU Acute Peppers ( Florida) 0.87 2.69 ( 6) 0.26 ( 6) 25.2 Almonds ( California) 0.56 7.17 ( 4) 0.69 ( 4) 13.9 Data indicated that the highest peak value from modeling is 25.2 ppb ( FL peppers scenario) after adjustment by the 0.87 national PCA. This value is assigned to be the high limit to the acute EDWC range; therefore the range is 0.1 ppb ( from monitoring) to 25.2 ppb ( from modeling). It is noted however, that the high limit of the range is reduced from 25.2 to 13.9 ppb ( CA almonds scenario) after adjustment by associated regional PCA.

Table 4 summarizes modeling results for all runs, at both the national and regional scales, for scenarios representing monitored and non monitored areas of the country.

Table 4. PRZM/ EXAMS values for the EDWCs of ETU from surface water.

State Crop Number of monitored Sites \ Representative Crop Scenario EDWCs ( ppb) Adjusted by the National PCA of 0.87 EDWCs ( ppb) Adjusted by the Regional PCA 1 Acute Chronic/ Non cancer Chronic/ Cancer Acute Chronic/ Non cancer Chronic/ Cancer I. Monitored EBDCs Use Patterns ( Areas/ Crops)

ME Potatoes 5 ME potatoes 8.9 0.9 0.8 1.4 0.1 0.1 NY Apples 5 PA apples 18.3 1.3 1.1 9.7 0.7 0.6 MI Apples 3 Mixed grapes/ apples ( two sites) and mixed grapes/ nursery plants ( one site): No Scenarios are available MN Potatoes 2 ME potatoes 8.9 0.9 0.8 1.4 0.1 0.1 ID potatoes 6.0 0.7 0.6 4.4 0.5 0.4 WA Apples 4 OR apples 16.0 1.2 1.1 11.6 0.9 0.8 Overall 06 18 0.7 1.3 0.6 1.1 01 12 0.1 0.9 0.1 0.8 I. Un monitored EBDCs Use Patterns ( Areas/ Crops)

PRZM/ EXAMS Scenarios ( States/ Use Patterns) EDWCs ( ppb) Adjusted by the National PCA of 0.87 EDWCs ( ppb) Adjusted by the Regional PCA 1 Acute Chronic/ Non cancer Chronic/ Cancer Acute Chronic/ Non cancer Chronic/ Cancer 87 ( 1) Highest values: FL peppers; NC apples; FL sweet corn, tomatoes & turf; CAalmonds; PA tomatoes; CA onions; NC peanuts; CA grapes; and FL cabbage. 10 25 0.7 1.9 0.5 1.8 04 14 0.3 1.2 0.2 1.1 ( 3) Lowest values: MN sugar beet; TX wheat; CA tomatoes; OR sweet corn & wheat; and ND wheat. 05 09 0.2 0.9 0.2 0.8 01 09 0.1 0.7 0.1 0.6 Overall 05 25 0.2 1.9 0.2 1.8 01 14 0.1 1.2 0.1 1.1 As shown in Table 4, PRZM/ EXAMS runs predicted EDWCs for ETU to be between 5 25 ppb and chronic values between 0.2 1.9 ppb whereas two years targeted monitoring fails to show any detection over the detection limit of 0.1 ppb. Compared to the monitoring based single 0.1 ppb chronic/ non cancer and chronic/ cancer value, modeling results indicate that the range of national scale chronic values is 0.2 1.9 ppb for chronic/ non cancer and 0.2 1.8 ppb for chronic/ cancer. The range for these two values are reduced, at the regional level to 0.1 1.2 ppb for chronic/ non cancer and 0.1 1.1 ppb for chronic/ cancer.

As shown in the attached GIS maps ( Attachment 1), not all possible surface water sites were monitored. Therefore, acute/ chronic values obtained for monitored areas were compared to other areas of the country where surface water monitoring was not conducted. The comparison reveals that PRZM/ EXAMS predicted acute/ chronic ETU/ EDWCs for scenarios relevant to use patterns of monitored are relatively higher than those for un monitored sites ( Table 4). In order to further examine the data in leu of the non detection of ETU, the following assumptions were made:

( 1) The chronic value of 0.1 is an acceptable value for monitored sites; and ( 2) The change in chronic long term values is similar to that of the acute ( long term) values. Examination of the chronic/ acute results for the 22 runs suggested that the assumption for these runs is reasonable. A plot of acute and chronic concentrations for the current runs reveals a linear relationship with a reasonable R2 value of 0.58 ( Figure 1). 88 0 5 10 15 20 25 30 Peak EDWCs for ETU ( ppb) 0 0.5 1 1.5 2 Chronic EDWCs for ETU ( ppb)

R square = 0.584 # pts = 22 y = 0.278 + 0.0469x Chronic Vs. Peak Values Figure 1. A plot of the relationship between acute and chronic values from 22 PRZM/ EXAMS runs.

Based on these assumptions, the maximum national/ regional acute/ chronic values for monitored areas are adjusted proportionally by a factor of 0.0769 ( 0.1 ppb/ 1.3 ppb) so that the maximum chronic value for monitored sites is equal to 0.1 ppb. Table 5 shows original and adjusted acute/ chronic ETU/ EDWCs predicted by PRZM/ EXAMS for scenarios relevant to use patterns of monitored and un monitored sites.

Table 5. Range of original and adjusted values for PRZM/ EXAMS acute/ chronic ETU/ EDWCs.

Sites National EDWCs ( ppb) Regional EDWCs ( ppb)

Acute Chronic Peak Chronic ( 1) Monitored Original PRZM/ EXAMS values 06 18 0.7 1.3 01 12 0.1 0.9 Adjusted PRZM/ EXAMS values < 1 01 < 0.1 0.1 < 1 01 < 0.1 0.1 ( 2) Un monitored Original PRZM/ EXAMS values 05 25 0.2 1.9 01 14 0.1 1.2 Adjusted PRZM/ EXAMS values < 1 02 < 0.1 0.2 < 1 01 < 0.1 0.1 Adjusted values are much lower than the original results from PRZM/ EXAMS and the chronic values from all runs are near the assigned value of 0.1 ppb. Additionally, the maximum value of the assigned bracketed range of the acute ( 0.1 25 ppb) becomes one order of magnitude smaller at both the national ( 0.1 2 ppb) and the regional scales ( 0.1 1 ppb).

Surface water targeted monitoring fails to show any detection of ETU above the detection limit 0.1 ppb, however, ETU/ EDWCs predicted by PRZM/ EXAMS were higher. Reasons that may be given to explain these results include: 22 Blazquez, C. H. 1973. J. Agric. Food Chem. 21 ( 3), 330 332.

89  Adjustment of PRZM/ EXAMS estimates using PCA values higher than those actually found for some crops;

 In modeling, it was assumed that EBDC parents degrade rapidly and totally to ETU. This is because currently approved version of PRZM is only capable of simulating pesticide metabolites through such simplified assumption giving a relatively high uncertainty in the ETU estimates. Fate data for ETU suggest maximum ETU attained in the natural environment is a result of two major processes: formation and degradation. This maximum is expected to occur shortly after the parent reaches the aquatic system by drift and much longer after foliar applied parent reaches the soil system.

 In modeling, the maximum observed conversion of parent to ETU was used ( 23.6% for water/ sediment systems and 9.6% for the aerobic soil systems). Respective observed minimum values were much lower ( 1.0% for the aerobic soil systems and 14.9% for water/ sediment systems);

 The choice of the date for the first application affects the concentrations estimated by PRZM/ EXAMS; EFED selected dates based on information present in the label. EBDCs are applied as protectant fungicides for diseases that appear early and/ or late in the season. In most cases, label application dates were set based on the crop growth stage which was used by EFED to choose the appropriate window for the first application.

 The apparent non sensitivity of PRZM/ EXAMS simulations for the photolysis half life of ETU. Indirect photolysis is reported to be the main reason for non detection of ETU in surface waters22. However, changing the photolysis half life from stable to 1 day appears not to affect resultant concentrations from PRZM/ EXAMS. For example, FL peppers photolysis half life of 1 day gave concentrations of 25.2 ppb for the acute, 1.1 ppb for the chronic/ non cancer and 0.7 ppb for the chronic/ cancer. When photolysis half life is changed to stable the results were the same for chronic values and almost the same for the acute value ( 25.4 ppb compared to 25.2 ppb).