Modeling estimates using PRZM EXAMS are also estimating EBDC complex by predicting the EECs using the physicochemical properties of the EBDC, parent aerobic soil metabolism half lives and sorption coefficients. Appendix VII shows the toxicity to aquatic organisms found from the various EBDC aquatic toxicological studies. These endpoints are an estimate of the EBDC complex that fixes the toxicities ( that is, LC 50 s, EC 50 s, and NOAECs). The modeling EECs are also estimates. Influences such as particle size, conditions of storage, degree of decomposition, pH, and the presence of other cations ( see Figure VI 1) would always cause difficulty in providing definite aquatic toxicological endpoints for the EBDCs. 33 Table VI 1: Toxicological Endpoints Used to Determine Aquatic Risk Quotients ( RQs) for Metiram Type of Toxicity Organism Species Toxicological Endpoint Acute Freshwater fish rainbow trout ( Salmo gairdneri) LC 50 = 230 ppb Chronic no data no data Acute Freshwater invertebrate waterflea ( Daphnia magna) LC 50 > 358 ppb 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 ( Ankistrodesmus bibraianus) EC 50 = 77 ppb b. Exposure and Risk Quotients EFED performed Tier II modeling ( PRZM/ EXAMS) for metiram's use on apples and potatoes, the main crop uses for metiram. Modeling values used ( Table V 1) and resulting EECs ( Table V 2) for Tier II modeling are in section V Water Resource Assessment, above.

EFED did not evaluate acute risks to estuarine/ marine animals because of the lack of data ( acute toxicity endpoints). EFED did not evaluate chronic risks for freshwater aquatic animals from exposure to the metiram complex because no data ( chronic toxicity endpoints) were available to evaluate these risks. EFED is requiring these missing data through this document. EFED is reserving the need for chronic studies, for estuarine/ marine aquatic organisms, until EFED receives and reviews the acute studies for estuarine/ marine organisms. Chronic assessments to nontarget aquatic plants are not currently being performed. Below ( figure VI 2) are graphs representing metiram's acute aquatic risks to freshwater fish and nonvascular aquatic plants from exposure to the metiram complex. EFED bases these potential risks on metiram's current use patterns at maximum application rates, maximum number of applications allowed each growing cycle or year, minimum intervals between applications and maximum predicted EECs from modeling. For a more detailed listing and explanation of metiram's risk, see Appendix IV. 34 0 0.2 0.4 0.6 0.8 1 1.2 1.4 Risk Quotient Apples Potatoes Sites Acute RQ for Nonvascular Aquatic Plant Acute RQ for Freshwater Fish Metiram Acute Aquatic Risk Based on Tier II PRZM EXAMS Modeling Figure VI 2 RQ greater or equal to 1.0 exceeds aquatic plant acute and acute endangered species LOCs. RQ greater or equal to 0.5 exceeds aquatic animal acute, acute restricted use and acute endangered species LOCs. RQ greater or equal to 0.1 exceeds aquatic animal acute restricted use and acute endangered species LOCs RQ greater or equal to 0.05 exceeds aquatic animal acute endangered species LOCs There are no known nonvascular aquatic plant species on the endangered species list. 35 Figure VI 3  Frequency of Organism Classes in Reported Incidents in EIIS ( Mastrota, 2001) c. Aquatic Risk Assessment The limited acceptable ecotoxicological data and numerous data gaps for metiram as well as it's major toxicological degradate of concern, ETU ( see ETU chapter), makes it impossible to render a complete assessment concerning metiram's potential aquatic environmental risk. Based on limited data, metiram is likely to pose a potential acute restricted use and acute endangered species risk to freshwater fish ( highest RQ = 0.43 for freshwater fish on apple use) and an acute risk to nonvascular aquatic plants ( highest RQ = 1.28 from metiram's use on apples) since risk LOCs have been exceeded ( see Figure VI 2). No adverse aquatic incidents concerning metiram's use ( see below) have been reported. The major uncertainties concerning metiram's risk to aquatic organisms revolves around the lack of data and in particular the lack of chronic data. The data being used to assess the risk to aquatic nonvascular plants is supplemental and core data is needed. Additional aquatic plant studies need to be submitted for a vascular aquatic plant, a marine diatom, a blue green algae and a freshwater diatom to fully evaluate metiram's risk to aquatic plants. Core studies to evaluate the acute risks to estuarine/ marine organisms need to be submitted and there are no chronic studies available upon which to conduct aquatic chronic risk assessments for metiram.

i. Incidents The Ecological Incident Information System ( EIIS) indicated there were no adverse aquatic incidents reported in association with metiram use.

Although more than 50% of the incidents reported in EIIS deal with plant and fish issues ( see Figure VI 3), most of the plant incidents involve spray drift damage to terrestrial plants and most of the fish incidents are fish kill reports. Chronic problems that affect wildlife from the use of metiram and it's degradate, ETU, would be expected to be largely unnoticed in the field and thus incident reports, as a result of chronic exposure, would not be expected. Since metiram has been used in the US since 1983, the lack of metiram reported aquatic related incidents would support the expectation that metiram is a low acute aquatic risk concern. However, EIIS would not be expected to p r o vide info rma t io n concerning chronic problems associated with pesticidal use in the environment. 36 ii. Endocrine Disruptors Metiram's aquatic toxicological data are limited to acute testing, based on mortality effects. Evaluating metiram's effects on aquatic organisms for endocrine induced effects is uncertain. EFED needs more testing over more taxa to evaluate metiram's potential to act as endocrine disruptors in aquatic organisms.

iii. Endangered Species Based on available screening level information there is a potential concern for acute effects on listed freshwater fish species should exposure actually occur. The Agency does not currently have data on which to fully evaluate the toxicity of metiram to endangered/ threatened species of freshwater organisms, estuarine/ marine organisms, or aquatic vascular plants. To date, there are no known nonvascular aquatic plant or estuarine/ marine invertebrate species on the endangered species list. 37 VII. Terrestrial Exposure and Risk a. Hazards Summary ( Acute/ Chronic)

Acutely, metiram is practically nontoxic to birds ( Northern bobwhite quail acute oral LD 50 > 2,150 mg/ kg). Avian subacute dietary tests were conducted using Northern bobwhite quail and mallard duck as test species. The formulated product LC 50 values for bobwhite and mallard were 4,640 ppm ( 3,712 ppm ai ) and > 4,640 ppm (> 3,712 ppm ai ), respectively. This classifies metiram as slightly toxic to avian species from subacute dietary exposure.

In a metiram avian reproduction study using the mallard duck, chronic toxic effects were seen. These effects in birds included: reduced egg production; reduced mean egg weight; reduced fertility rate; reduced number of hatched ducklings; reduced number of 14 day old survivors; and an increased rate of early embryonic deaths. The reproduction NOAEC/ LOAEC is 50/ 300 ppm. EFED classified a Northern bobwhite quail reproduction study as supplemental because of mortality and a high number of cracked eggs (> 18%) in the control group. A NOAEC of > 500 ppm was established at the highest dose tested in this study ( MRID No. 41082001) with no LOAEC determination because no adverse effects were noted at the concentrations tested. A waiver for additional reproductive testing on Northern bobwhite quail was requested ( Barcode No. D223505; 3/ 96) based on similarity to testing results for the EBDC's, and the registrant was informed testing would be held in abeyance and reconsidered at reregistration. Collectively, the mallard is the more sensitive species for the EBDCs, and EFED will use results from the mallard reproductive study for risk assessment purposes. Therefore, a repeat of this study ( MRID No. 41082001) is not necessary.

Acutely, metiram is practically nontoxic to small mammals with an oral LD 50 > 5,000 mg/ kg in tests done on laboratory rats. Results from a chronic 3 generation reproduction study in rats for metiram show a parental and reproductive toxicity at a LOAEL of 320 ppm ( NOAEL = 40 ppm). Parental toxicity resulted in decreased body weight during gestation and lactation for females. Reproductive toxicity resulted in decreased mating performance ( increased precoital time) in the F2 generation ( two generations removed from the original parent generation).

Currently, EFED does not assess risk to non target insects using risk quotients. Results of acceptable studies are used for recommending appropriate label precautions. Since metiram was determined to be practically nontoxic to honey bees ( LD 50 = 437 µ g/ bee) no bee precautionary labeling is required on metiram product labeling.

EFED has not received any nontarget terrestrial plant studies and is unable to assess the risk to nontarget terrestrial plants as a result of metiram's uses. The submission of Tier I seedling emergence and vegetative vigor studies for a TEP are needed to evaluate this risk.

For a more detailed listing and explanation of metiram's hazards to all terrestrial organisms, see Appendix III. 38 Table VII 1: Toxicological Endpoints Used to Determine Risk Quotients ( RQs) for Metiram Type of Toxicity Organism Species Toxicological Endpoint Subacute dietary Bird Northern Bobwhite Quail ( Colinus virginianus) LC 50

3,712 ppm Chronic Bird mallard duck ( Anas platyrhynchos) NOAEC = 50 ppm1 Chronic Mammal laboratory rat ( Rattus norvegicus) NOAEL = 40 ppm2 1 LOAEC based on reduced egg production, reduced mean egg weight, reduced fertility rate, reduced number of hatched ducklings, reduced number of 14 day old survivors; and an increased rate of early embryonic deaths 2 Reproductive study LOAEL based on parental toxicity resulting in decreased body weight during gestation and lactation for females and reproductive toxicity resulting in decreased mating performance ( increased precoital time) in the F2 generation ( two generations removed from the original parent generation).

b. Exposure Summary EFED evaluated terrestrial exposure using 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 initial concentrations on plant surfaces based on Kenaga predicted maximum and mean residues as modified by Fletcher et al. ( 1994) and assumes 1st order dissipation. Kenaga estimates and an explanation of the model with sample output are presented in Appendix VII. Without available total foliar dissipation half life data for metiram, EFED used a 35 day half life. EFED based this half life selection on the upper limit of pesticide, foliar dissipation half lives provided in the half life listing of Willis and McDowell, 1987. EFED uses this value as a default value when the foliar dissipation for a particular pesticide is unknown.

c. Risk Quotients Below are graphs representing metiram's potential acute and chronic risks to nontarget terrestrial animals. These potential risks are based on metiram's current use patterns at maximum application rates and minimum intervals between applications. These graphs show the acute and chronic Risk Quotients ( RQs) that can be expected from terrestrial animals feeding on the food items listed. These acute and chronic RQs are derived from estimated environmental concentrations ( EECs) based on the maximum and mean residue estimates ( see Appendix II) that are expected on these food items following metiram's applications to various sites indicated.

Metiram's avian acute dietary RQs exceed acute, acute restricted use and acute endangered species LOCs for tobacco, apple, and potato uses. The RQs range from 0.56 to 1.22 ( see Figure VII 1, below). Avian acute endangered species levels of concern ( LOCs) are exceeded for all metiram use patterns at maximum EEC levels ( RQ range from 0.11 to 1.22). The chronic RQs for multiple broadcast spray applications of metiram are tabulated below in Figure VII 2. The results show, for multiple spray applications of metiram, the avian chronic LOCs are exceeded for all uses patterns. RQs exceed chronic LOCs ranging from a high of 91 from the tobacco use to a low of 1 from metiram's uses on potatoes and ornamental nonflowering plants.

Chronic concerns to terrestrial animals are exceeded when the RQ reaches 1.0. For example, the chronic RQ for birds feeding on short grass as a result of metiram being applied to tobacco is 91 at maximum residue levels and 32 at mean residue levels. As can be seen from these graphs, nearly all 39 0 0.2 0.4 0.6 0.8 1 1.2 1.4 Risk Quotient ( RQ)

Tobacco Apples Potatoes Ornamental ( nonflowering plants) Ornamental ( woody shrubs & vines)

Sites Max. for Short grass Max. Broadleaf/ ForagePlants/ Sm. Insec Max. for Tall grass Mean for Short grass Mean Broadleaf/ ForagePlants/ Sm. Inse Mean for Tall grass Max. Fruits/ Pods/ Seeds/ Large Insects Mean Fruits/ Pods/ Seeds/ Large Insects Metiram Acute Avian Risk Maximum and Mean Exposure Risk Figure VII 1 RQ greater or equal to 0.5 exceeds acute, acute restricted use and acute endangered species LOCs. RQ greater or equal to 0.2 exceeds acute restricted use and acute endangered species LOCs RQ greater or equal to 0.1 exceeds acute endangered species LOCs. metiram's uses exceed chronic LOCs for birds and mammals. Based on the estimated mean residues on fruits, pods, seeds, and large insects the avian and mammalian chronic LOCs would not be exceeded as a result of metiram's use on ornamentals. The chronic exceedances to birds range from a high RQ of 91 on tobacco to a low of 1 on ornamentals. For mammals ( Figure VII 3), the range of RQ exceedance is from a high of 113 on tobacco to a low of 1 on ornamentals.

For a more detailed listing and explanation of metiram's risk to all terrestrial organisms, see Appendix IV. 40 1 10 100 Risk Quotient ( RQ)

Tobacco Apples Potatoes Ornamental ( nonflowering plants) Ornamental ( woody shrubs & vines) Sites Mean Fruits/ Pods/ Seeds/ Large Insects Max. Fruits/ Pods/ Seeds/ Large Insects Mean for Tall grass Mean Broadleaf/ ForagePlants/ Sm. Insects Mean for Short grass Max. for Tall grass Max. Broadleaf/ ForagePlants/ Sm. Insects Max. for Short grass Metiram Chronic Avian Risk Maximum and Mean Exposure Risk Figure VII 2 ( Based on a 35 day foliar dissipation half life) RQ greater or equal to 1 exceeds chronic LOCs. 41 1 10 100 1000 Risk Quotient ( RQ)

Tobacco Apples Potatoes Ornamental ( nonflowering plants) Ornamental ( woody shrubs & vines)

Sites Mean Fruits/ Pods/ Seeds/ Large Insects Max. Fruits/ Pods/ Seeds/ Large Insects Mean for Tall grass Mean Broadleaf/ ForagePlants/ Sm. Insects Mean for Short grass Max. for Tall grass Max. Broadleaf/ ForagePlants/ Sm. Insects Max. for Short grass Metiram Chronic Mammalian Risk Maximum and Mean Exposure Risk Figure VII 3 ( Based on a 35 day foliar dissipation half life) RQ greater or equal to 1 exceeds chronic LOCs. 42 Metiram's Residue from Apple Use Based on Fate v. 5 Modeling 1 10 100 1000 10000 1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 55 58 Day ppm Metiram's Avian NOAEC = 50 ppm Metiram's Mammalian NOAEL = 40 ppm Maximum Residue on Short Grass Maximum Residue on Broadleaf / Forage Plants & Small Insects Maximum Residue on Tall grass Mean Residue on Short grass Mean Residue on Broadleaf / Forage Plants & Small Insects Mean Residue on Tall grass Maximum Residue on Fruits, Pods, Seeds, and Large Insects Mean Residue on Fruits, Pods, Seeds, and Large Insects Figure VII 4 d. Terrestrial Risk Assessment A dose response slope value for the bobwhite quail acute dietary toxicity ( that is, LC 50 = 3,712 ppm metiram) was not determined. In this dietary toxicity study, 5 of 10 birds died at the highest concentration tested with no mortality at the lower concentrations tested. Since only one concentration provided a percent mortality between 0 and 100%, a slope value could not be determined through probit analysis. Lacking slope information, EFED was not able to predict the likelihood of individual acute effects in birds, from metiram's exposure.

Approximately 460,000 lbs ai of metiram is applied annually to US apples with 11% of the total apple, U. S. planted, acres being treated with metiram ( EPA use data 1992 through 2001) ( BEAD's Quantitative Usage Analysis for Metiram dated November 1, 2002). Metiram can be applied 4 times per season every 7 days from pre bloom through the foliar stages of apples. Bear, ruffed grouse, snowshoe hare, pheasants, Hungarian partridges, cottontail rabbits, deer, fox, opossums, raccoons, fox squirrels, songbirds, and elk feed on apple fruit and/ or foliage ( Gusey and Maturdo, 1972). Upland gamebirds such as ruffed grouse and ring necked pheasant feed on apple fruit, seeds and buds.

Songbirds such as chestnut backed chickadees, red shafted flickers, robins, starlings, varied thrushes, tufted titmouse, cedar waxwings and Lewis woodpeckers feed on apple fruit and seeds. Fur and game mammals such as black bears, foxes, yellow bellied marmots, porcupines, cottontail rabbits, and red squirrels feed on apple fruit and bark with hoofed browsers such as white tailed deer feeding on apple fruit, twigs and leaves ( Martin et. al., 1961). Birds such as morning doves and valley quail utilize apple orchards for nesting and brood rearing ( Gusey and Maturdo, 1972). These wildlife 9 Rate reductions determined by randomly imputing application rates into ELL Fate spreadsheet program until the mammalian chronic risk to 15 gram body weight small mammal from metiram residues on short grass is less than or equal to 1.

43 activities in apple orchards occur throughout the year. Figure VII 4 shows the residue levels ( ppm) that can be expected on various avian and mammalian food items as a result of metiram's use on apples. These metiram residues are based on metiram being applied 4 times every 7 days at a maximum application rates ( 4.8 lb ai/ A). This figure also shows the NOAEC ( 50 ppm) for birds and the NOAEL ( 40 ppm) for mammals as horizontal lines. Metiram levels at or above these horizontal lines pose a potential risk of adverse reproductive effects to the birds and mammals feeding on these food items. For birds and mammals this potential risk begins on Day 1 when metiram range from 72 ppm on fruits, pods, seeds, and large insects to 1,152 ppm on short grass for any and all food items the birds may ingest and continues throughout the apple production season or for more than 58 days. On Day 58 the metiram would range from 54 ppm as the mean residue on fruit, pods, seeds, and large insects to 1,857 ppm as the maximum residue on short grass. Although apples is being used as an example of the wildlife exposure that can be expected from metiram's registered use, all the sites metiram is currently being used on ( see Table II 1) would have comparable exposure levels with similar potential risks to wildlife.

In this screening level assessment, metiram's high application rates combined with repeat applications are a major reason why avian and mammalian LOCs are exceeded. Single application rates range from 1.2 lb ai/ A on Ornamentals ( woody shrubs & vines) to 6.8 lb ai/ A on tobacco. Labeling allows repeat applications at these maximum rates for all metiram's uses. These high applications rates with repeat applications increases the exposure of metiram to nontarget organism. High exposure is the reason for high RQs. One way to grasp the impact of the high exposure is to use modeling to estimate the reductions needed to reduce the EECs below the LOCs. Using modeling to calculate EECs below LOCs is simply a rough estimate but does provide some insight into the extent metiram's application rates contributes to potential chronic risk to birds and mammals.

To reduce the exposure to birds and mammals from metirams's use on apples, the maximum single application rate would need to be reduced from the current 4.8 lb ai/ A to 0.05 lb ai/ A ( see figure VII 5) 9. This calls for a 96 fold decrease in the maximum application rate of metiram to apples. A combination of rate drops with a decrease in the number of applications per growing season, could also be used to lessen the EECs. However, to reduce the potential chronic EEC exposure risk, essentially only 1 metiram application could be made to apples at a maximum application rate of 0.17 lb ai/ A ( see figure VII 6). This translates to a 28 fold application rate decrease and cuts out all multiples applications. Current labeling allows 4 metiram applications to apples. 44 Metiram Chemical Name: Apples Use non granular Formulation Inputs lbs a. i./ acre 0.05 Application Rate days 35 Half life days 7 Application Interval 4 Maximum # Apps./ Year Outputs 56 Day Average Maximum Concentration Concentration ( PPM) ( PPM) 25.74 39.46 Short Grass 11.80 18.08 Tall Grass 14.48 22.20 Broadleaf plants/ Insects 1.61 2.47 Seeds 4650 Acute LC50 ( ppm) Avian 50 Chronic NOAEC ( ppm)

Chronic RQ Acute RQ ( Max. res. mult. apps.) 0.79 0.01 Short Grass 0.36 0.00 Tall Grass 0.44 0.00 Broadleaf plants/ Insects 0.05 0.00 Seeds 5000 Acute LD50 ( mg/ kg) Mammalian 40 Chronic NOAEL ( mg/ kg 1000 g mammal 35 g mammal 15 g mammal Chronic RQ Chronic RQ Chronic RQ ( Max. res. ) Acute RQ ( Max. res. ) Acute RQ ( Max. res. ) Acute RQ mult. apps.) ( mult. apps) mult. apps.) ( mult. apps) mult. apps.) ( mult. apps) 0.15 0.00 0.65 0.01 0.94 0.01 Short Grass 0.07 0.00 0.30 0.00 0.43 0.00 Tall Grass 0.08 0.00 0.37 0.00 0.53 0.00 Broadleaf plants/ Insects 0.01 0.00 0.04 0.00 0.06 0.00 Seeds Figure VII 5: Metiram Mitigation Based on Reduction in Application Rate to Apples. ( Libelo. 1999) 45 Metiram Chemical Name: Apples Use non granular Formulation Inputs lbs a. i./ acre 0.17 Application Rate days 35 Half life days 7 Application Interval 1 Maximum # Apps./ Year Outputs 56 Day Average Maximum Concentration Concentration ( PPM) ( PPM) 24.90 40.80 Short Grass 11.41 18.70 Tall Grass 14.01 22.95 Broadleaf plants/ Insects 1.56 2.55 Seeds 4650 Acute LC50 ( ppm) Avian 50 Chronic NOAEC ( ppm)

Chronic RQ Acute RQ ( Max. res. mult. apps.) 0.82 0.01 Short Grass 0.37 0.00 Tall Grass 0.46 0.00 Broadleaf plants/ Insects 0.05 0.00 Seeds 5000 Acute LD50 ( mg/ kg) Mammalian 40 Chronic NOAEL ( mg/ kg)

1000 g mammal 35 g mammal 15 g mammal Chronic RQ Chronic RQ Chronic RQ ( Max. res. ) Acute RQ ( Max. res. ) Acute RQ ( Max. res. ) Acute RQ mult. apps.) ( mult. apps) mult. apps.) ( mult. apps) mult. apps.) ( mult. apps) 0.15 0.00 0.67 0.01 0.97 0.01 Short Grass 0.07 0.00 0.31 0.00 0.44 0.00 Tall Grass 0.09 0.00 0.38 0.00 0.55 0.00 Broadleaf plants/ Insects 0.01 0.00 0.04 0.00 0.06 0.00 Seeds Figure VII 6: Metiram Mitigation Based on Reduction in Application Rate and Number of Applications to Apples. ( Libelo. 1999)

Besides metiram's use on apples, metiram is also used on potatoes, tobacco, ornamental nonflowering plants and ornamental woody shrubs and vines ( see Table II 1, above). Each of these groupings represent a unique use pattern. The potential exposure cuts, using apples as an example, could be extended to each of these separate crop groupings. The conclusions for these other crop groupings would be similar to the conclusions drawn from the example of metiram's use on apples. In other words, all metiram's uses represent a potential extended chronic risk to birds and mammals. Decreases in the amounts of metiram applied would need to be large to allay metiram's potential chronic risk to birds and mammals. The temporal chronic risks to birds and mammals from metiram's current uses are provided in Table VII 2. As with the apple use, the potential chronic risks to birds and mammals begins with the first application of metiram to the crop or site and continues throughout the crop/ site cycle. In Table VII 2, the times of potential extended chronic risks to birds and mammals is based on maximum application rates, maximum number of applications and minimum intervals between application. As can be seen from the range of metiram on avian and mammalian 46 food items ( Table VII 2), the potential risk to birds and mammals extends across all food items at maximum or mean residue levels.

Table VII 2. Temporal Chronic Risks as a Result of Metiram on Avian/ Mammalian Food Items. 1 Crop Number of Days Metiram Exceed Birds' Chronic NOAEC ( 50 ppm) & Mammals' Chronic NOAEL ( 40 ppm) ( days) Range of Average, Daily, Maximum Metiram on Short Grass to Average, Daily, Mean Metiram residues on Fruits, Pods, Seed & Large Insects ( ppm)

Apples > 58 2,451 to 71 for 58 days Potatoes > 65 1,310 to 38 for 65 days Tobacco2 > 42 3,138 to 92 for 42 days Ornamentals ( nonflowering plants) 2 > 51 667 to 19 for 51 days Ornamentals ( woody shrubs & vines) 2 > 51 500 to 15 for 51 days 1. Based on FATE v 5.0 modeling with a total foliar residue half life of 35 days. 2. Maximum number of applications/ year or crop cycle not specified on labeling. Assumed 3 applications per crop cycle.

It is unknown if the scenario chosen for tobacco is truly " typical". Selection could have been based on the label specification to make two applications per week from seedling stage to transplant. Assuming 70 75 days from planting seeds to transplant, 10 14 days from seed to plant emergence, and 2 applications per week over the period of plant growth in the beds, the number of applications could be as high as 16. The assumption in this risk assessment assumed 3 applications during the crop cycle and even at this low number of applications the use of metiram on tobacco exceeds both acute and chronic LOCs. As shown in Figure VII 1, above, acute avian LOCs are exceeded. As shown in Figures VII 2 and VII 3, chronic LOCs are greatly exceeded for birds and mammals.

The avian acute and chronic RQ values are exceeded for all scenarios. Metiram's avian acute RQ exceedances are due mainly to exposure estimates. Acutely, metiram is only slightly toxic ( Bobwhite quail LC 50 = 3,712 ppm) to birds. Metiram's chronic RQ exceedances are triggered on toxicity ( mallard duck NOAEC = 50 ppm) and exposure. However there is a degree of uncertainty in the exposure values used. In the modeling, EFED assumed a total foliar residue dissipation half life of thirty five ( 35) days. EFED used this value as a default value because metiram's total foliar residue half life is unknown. Uncertainty exists because metiram ( complete polymeric chains) is nonpersistentt in most of the natural environments. EFED expects metiram to decompose rapidly ( within days) by hydrolytic reactions in the main compartments of the natural environment. Whereas soil/ sediment associated residue appear to biodegrade at a slow rate producing metiram degradates including ETU. EFED expects hydrolytic breakdown of metiram because most plant disease problems are the result of rain events and metiram ( a fungicide) would be applied between these rain events to plant surfaces for disease control. Data from laboratory studies show metiram may degrade rapidly. However, there are supplemental data that suggests that terrestrial field dissipation ( DT 50 ) for metiram can range from 20 to 143 days. Finally, the need for frequent reapplications ( at 4 to 7 day intervals) of metiram provides grounds that protective nature of metiram is limited pointing to added uncertainty in assuming a 35 day half life.

EFED understands the 35 day TFR half life used in calculating avian and mammalian RQs represents an uncertainty because metiram's TFR half life range is unknown. DFR and TFR values for maneb and mancozeb ( two EBDCs chemically related to metiram), indicates 3 days may be an approximate low end foliar dissipation half life estimate for the EBDCs in general. EFED provides a brief 47 1 10 100 Risk Quotient ( RQ)

Tobacco Apples Potatoes Ornamental ( nonflowering plants) Ornamental ( woody shrubs & vines)

Sites Mean Fruits/ Pods/ Seeds/ Large Insects Max. Fruits/ Pods/ Seeds/ Large Insects Mean for Tall grass Mean Broadleaf/ ForagePlants/ Sm. Insects Mean for Short grass Max. for Tall grass Max. Broadleaf/ ForagePlants/ Sm. Insects Max. for Short grass Metiram Chronic Avian Risk Maximum and Mean Exposure Risk Figure VII 7 ( Based on 3 day foliar dissipation half life) RQ greater or equal to 1 exceeds chronic LOCs. discussion of the foliar half life values ranges for maneb and mancozeb in Section II Introduction, Subsection iii Analysis Plan. For comparative purposes, EFED also provided an estimate of metiram's risk to birds and mammals based on a 3 day TFR half life value ( see Appendix IV).

Revised modeling, using a 3 day foliar dissipation half life for metiram, yields the avian chronic RQs shown in Figure VII 7. When compared with the chronic RQs provided in Figure VII 2 above, based on a 35 day foliar dissipation half life, potential chronic risks to birds still exist. This means EFED expects potential avian chronic risk from metiram's uses regardless of the foliar dissipation half life value used. EFED expects a similar result for the potential chronic risks to mammals ( see Appendix IV for RQs). A listing of avian and mammalian acute and chronic RQs for metiram based on a 3 day foliar dissipation half life can be found in Appendix IV.

EFED does not assess risk to non target insects using risk quotients. Results of acceptable studies are used for recommending appropriate label precautions. Since metiram was determined to be practically nontoxic to honey bees ( LD 50 = 437 µ g/ bee) no bee precautionary labeling is required on metiram product labeling. 48 EFED does not have sufficient data to evaluate metiram's risk to non target terrestrial plants. Tier I seedling emergence [ guideline 122 1( a)] and vegetative vigor [ guideline 122 1( b)] studies for metiram have not been received and submission of these studies for review by the EFED are recommended.

EFED expects metiram's potential acute risk to birds and mammals to be low. There are potential chronic risks to birds and mammals from metiram's use on apples, potatoes, tobacco seed beds ( although to a lesser extent for tobacco seed beds because of limited acreage) ornamental nonflowering plants, and ornamental woody shrubs and vines. EFED expects high potential chronic avian and mammalian risk from metiram's uses. The chronic RQs are exceeded as shown in Figures VII 2 and 3. Not only are the RQ values exceeded for the shortgrass scenario, but also for broadleaf plants, insects and seeds. Both maximum and mean EECs for these food items exceed avian and mammalian chronic LOCs for all metiram's uses. The number of days the terrestrial application residues exceed the avian chronic NOAEC ( 50 ppm) and mammalian chronic NOAEC ( 40 ppm) is also high ( from > 42 days on tobacco to > 65 days on potatoes, ( see table VII 2). Thus, it appears metiram's exposure is of sufficient magnitude and duration to pose a potential reproductive risk to both birds and mammals.

i. Incidents There are no incidents for metiram listed in the Ecological Incident Information System ( EIIS) data base dealing with adverse effects to terrestrial nontarget organisms.

Acutely, metiram, appears to pose a low risk to terrestrial animals. The chronic LOCs to terrestrial animals ( birds and mammals) are exceeded for all metiram use patterns. The incident reports filed with EPA mainly deal with field mortality of wildlife. EFED expects chronic problems affecting wildlife from the use of metiram would be largely unnoticed in the field. Because of this, EFED doesn't expect incident reports, from chronic exposure.

ii. Endocrine Disruption EPA is required under the Federal Food, Drug, and Cosmetic Act ( FFDCA), as amended by the Food Quality Protection Act ( FQPA), to develop a screening program to determine 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 that there was scientific basis for including, as part of the program, the androgen and thyroid hormone systems, in addition to the estrogen hormone system. EPA also adopted EDSTAC's recommendation that the Program include evaluations of potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA and, to the extent that effects in wildlife may help determine whether a substance may have an effect in humans, FFDCA authority to require the wildlife evaluations. As the science develops and resources allow, screening of additional hormone systems may be added to the Endocrine Disruptor Screening Program ( EDSP).

The avian reproductive studies reviewed by EFED noted metiram reproductive effects such as reduced egg production, reduced mean egg weight, reduced fertility rate, reduced number of hatched 49 ducklings, reduced number of 14 day old survivors, and an increased rate of early embryonic deaths. Metiram mammalian effects, from a reproductive study, were noted such as parental toxicity resulting in decreased body weight during gestation and lactation for females and reproductive toxicity resulting in decreased mating performance ( increased precoital time) in the F2 generation ( two generations removed from the original parent generation). In a 3 month feeding study submitted to The Agency ( MRID 42590 01), there was a significant decrease in total serum thyroxine ( T4) concentrations in both sexes of mice. These effects noted in both birds and mammals may be a result of hormonal disruption and might support the concern that metiram may be a potential endocrine disrupting compound. Based on these effects in birds and mammals, EFED recommends that when appropriate screening and/ or testing protocols being considered under the Agency's EDSP have been developed, metiram be subjected to more definitive testing to better characterize effects related to its endocrine disruptor activity.

iii. Endangered Species Based on available screening level information there is a potential concern for acute effects on listed birds species and chronic effects on listed birds and mammals should exposure actually occur. Even though metiram is only slightly toxic to birds, metiram's uses exceed the endangered species LOC ( RQ range from 0.11 to 1.22) at maximum EEC levels. EFED expects metiram poses a low acute risk to nontarget insects because metiram is practically nontoxic to honeybees, ( acute contact LD 50 = 437 µ g/ bee). Also, there is no incident data reporting adverse effects to honeybees from metiram's use. The Agency does not currently have enough data to perform a screening level assessment for metiram's effects on listed nontarget terrestrial plants. 50 APPENDIX I: Metiram Registered Uses & Notes on Fate Studies and Modeling a. Metiram Registered Uses Table 1. Registered uses for metiram.

Metiram Product Crop ( disease) Registered Maximum Application Rate and Application Methods Polyram 80 DF ( Dry Flowable)

( EPA Reg. No. 7969 105)

( Company: BASF) Apples ( Apple scab and apple rust) Pre bloom 4.8 lb ai/ acre ( max. seasonal total is 19.2 lb ai/ acre) 4 applications; 7 10 day application schedule through bloom; ground or aerial ( see note below this Table) or extended 2.4 lb ai/ acre ( maximum seasonal total 16.8 lb ai/ acre) 7 applications; 7 10 day application schedule; ground or aerial with chemigation permitted ( minimum of 5 GPA water by air) ( Do not combine pre bloom and extended schedules)

Potatoes ( Early and late blight) 1.6 lb ai/ acre ( max. seasonal total 11.2 lb ai/ acre) 7 applications; 5 10 day application schedule; not to exceed 2 applications per week Roses ( Cercospora leaf spot and black spot) 0.8 1.2 lb ai/ acre ( no max seasonal rate established) Weekly as needed; two applications per week if rainy; knapsack or other suitable small area spray equipment FL 980001 Polyram 80 DF Leatherleaf fern ( Anthracnose) 1.6 lb ai/ acre ( single weekly application); 0.8 lb ai/ acre ( 2 3 applications per week) weekly applications; increase to 2 3 apps per week if heavy disease pressure or periods of heavy rain ground application only; may use chemigation Potato Seed Treater Fungicide ( 7.04% dust)

( EPA Reg. No. 34704 731)

( Company: Platte Chemical Co.) Cut potato ( fusarium seed piece decay; seed borne common scab) 0.105 lb ai cwt ( cut seed pieces to average 1 3/ 4 to 2 ounces each; seed requirements will vary from 12.5 to 36 cwt per acre " 36 inch rows with seed pieces spaced 9 inches; cover seed pieces at least 4 inches"; 0.105 lb ai cwt X 36 cwt per acre is equivalent to 3.78 lb ai/ a)

Royal Brand Polyram 3.5 Dust Fungicide ( 3.5% dust)

( EPA Reg. No. 5481 264)

( Company: AMVAC) Tobacco seedling plants ( Blue mold) 6.776 lb ai/ acre ( 2 4 lb of product per 900 sq. ft.) 2 times weekly until transplant time; apply with a dusting machine that will give good coverage to plant 51 b. Notes on Fate Studies i. Aqueous medium studies Guidance for hydrolysis and aqueous photolysis require Parent EBDC to be applied at concentrations within the solubility range. It was established that any part of Parent EBDC that goes into solution will completely decompose, by hydrolytic reactions, into a suite of multi species residue; the EBDC complex. Reported levels of Parent EBDCs that decompose in water were near 2 ppm for metiram and in the range of 6 22 ppm for mancozeb and 6 200 ppm for maneb. Additionally, particle size reduction ( i. e. sonication) is believed to cause an increase in the level susceptibility of parent EBDCs to decomposition. In most studies, levels used in aqueous media studies were near this critical range of susceptibility, parent was determined by CS 2 and suspensions were prepared using ultrasonic. Therefore, calculated hydrolysis and/ or photolysis half lives are affected by:

( 1) Occurrence of hydrolytic decomposition during preparation of stock solution; indicated by the presence of high concentrations of transient species and degradates at time zero.

( 2) An increase of hydrolytic reactions caused by reduction of particle size by sonication; and ( 3) Nonspecificity of CS 2  determination for Parent EBDC in the presence of its hydrolytic complex because it was experimentally proven that CS 2 evolves from at least one of its constituents; EBIS.

( 4) influence of the presence of metal ions on solubility of Parent EBDC ( i. e decomposition to EBDC complex). These metal ions are introduced to the system from chemicals present in buffer solutions.

In studies were solvents DMSO is used, no half life could be calculated for EBDCs because no Parent EBDC would be present at time zero. This solvent appears to cause complete breakage of the EBDC complex into various transformation products dominated by ETU. This means that such study can only be used to identify effects of pH or photon energy and aging on the suite of EBDC complex present at time zero.

ii. Soil/ sediment studies Problems associated with soil sediment/ studies include:

( 1) Degradation of Parent EBDC, by decomposition in water, before time zero and when the application suspension is prepared. In most cases, resultant application suspensions were dominated by the EBDC complex. Analysis was not always performed for suspensions just before application.

( 2) Extraction systems ( i. e., acetonitrile/ water or methanol/ water) appear to affect the integrity of the parent. Therefore, resultant suite of EBDC complex ( in the extraction solution) was at least partly artificial and can not be used to represent the suite that might form in the environment. The use of different extraction systems made it difficult to compare results obtained from different soils.

( 3) EBDC complex has high affinity to soil and no characterization was conducted for the resultant bound species. Therefore, EBDCs bound species is suspicious of containing active species that can 52 0 7 14 Time ( days) 30.0% 40.0% 50.0% 60.0% 70.0% 80.0% 90.0%

Of Applied Radioactivity Loam ( Germany) LS ( Germany) Collamer SiL ( USA) Cashmere LS ( USA) Approximation 0 100 200 300 400 Time ( days) 50.0% 60.0% 70.0% 80.0%

Of Applied Radioactivity Loam ( Germany) LS ( Germany) Collamer SiL ( USA) Cashmere LS ( USA) Approximation be precursors for the degradate of concern ETU. For example, In metiram aerobic soil studies, bound species degraded after reaching a plateau in the range of 70 85%. Production of degradates and CO 2 , increased after the bound species reach the described plateau. Figure 1 shows bound radioactivity distribution with time as reported for soils in four aerobic soil studies.

( 4) Nonspecificity of CS 2  determination for Parent EBDC in the presence of its hydrolytic complex because it was experimentally proven that CS 2 evolves from at least one of its constituent; EBIS.

( 5) Chromatographic separation between Parent EBDC and various species in its complex was not conclusive and solvents used appear to affect the integrity of parent and some degradates and/ or transient species.

Figure 1. Change of bound radioactivity with time in four aerobic soils treated with metiram. 53 Therefore, the above mentioned difficulties should be taken in consideration in determining species present in fate studies and those expected to be present in the natural environment. For example, in metiram, it is expected that species present in fate studies are those shown in Figure 2 and those in compartments of the natural environment are those shown in Figure 3. 54 Metiram a. i Main consituents: Metiram " MT P" + Minor constituents: " MT C"

Air Water Run off " MT C" mainly ETU Metiram a. i with minimal change will eventually be deposited onto soil/ plant / water bodies Plant Metiram a. i can be affected by hydrolytic decomposition increasing " MT C" ( process is water availability and resident time dependent) Application " MT P"

Solid phase ( Soil particles)

" MT C" unkown sp. Drift Liquid phase ( Pore water)

" MT C" mainly ETU Solid phase ( Sediment particles)

" MT C" unkown sp. Liquid phase ( Water)

" MT C" mainly ETU Hydrolytic Decomposition Soil " MT P" Wash off Water Bodies " MT P"

Hydrolytic Decompos ition Erosion ( Adsorped " MT C" unknown species) Figure 3. Identity of various species expected to exist in various compartments of the natural environment. c. Notes on Modeling i. EECs for Parent metiram EECs for Parent metiram are presented in the Figure 4. Data for EECs were calculated using the slope of the line for 1.8 days ( Table IV. 2); the estimated hydrolysis half. Other assumptions included:

 Application rate of 4.8 lbs a. i/ Acre applied four times at 7 day intervals;

 All applied material reached the soil and mixed in the top 2" giving a zero time concentration of 7.1 ppm.

 Enough moisture is present to complete hydrolytic reactions.

Data indicate that soil EECs of metiram are expected to be below 1 ppm (. 14% of the applied) one day before the second application. The same is repeated after each of the four application causing an accumulation of nearly 0.6 ppm (. 9% of the applied) just before the last application. Amounts being left following all four applications degrades to negligible amounts within two weeks from the last application. This data are believed to represent concentrations in soil environments where most of the pesticide is applied. However, higher EECs are expected in dry conditions and in soils with very low water holding capacity. 55 0 7 14 21 28 35 42 Time ( days); Four Applications at days: 0, 7, 14 and 21 0 1 2 3 4 5 6 7 8 EECs of Metiram Parent ( ppm)

Parent EECs based on Hydrolysis half life= 1.8 days Considering that only a small fraction of the applied material would reach water bodies by drift, metiram complex, not parent, is the species expected to be found in water bodies affected by drift.

Figure 4. EECs for parent metiram following four applications of 4.8 lbs a. i/ acre applied four times at 7 day intervals.

ii. Background Information on the PRZM and EXAMS models & the Index Reservoir Scenario The linked PRZM and EXAMS models are used in this case as a second tier screen designed to estimate the pesticide concentrations found in water for use in drinking water assessments. They provide high end values on the concentrations that might be found in a small drinking water reservoir due to the use of pesticide. The Drinking Water Index Reservoir scenario includes a 427 acres field immediately adjacent to a 13 acres reservoir, 9 feet deep, with continuous site specific flow. This amount can be reduced due to degradation in field and the effect of binding to soil. Spray drift is equal to 6.4% of the applied concentration from the ground spray application and 16% for aerial applications.

The PRZM/ EXAMS modeling system with the Index Reservoir scenario also makes adjustments for the percent cropped area. While it is assumed that the entire watershed would not be treated, the use of a PCA is still a screen because it represents the highest percentage of crop cover of any large watershed in the US, and it assumes that the entire crop is being treated. Various other conservative assumptions of this scenario include the use of a small drinking water reservoir surrounded by a runoff prone watershed, the use of the maximum use rate and no buffer zone.

iii. Background Information on SCIGROW SCI GROW is a screening model which the Office of Pesticide Programs ( OPP) in EPA frequently uses to estimate pesticide concentrations in vulnerable ground water. The model provides an exposure value which is used to determine the potential risk to the environment and to human health from drinking water contaminated with the pesticide. The SCI GROW estimate is based on environmental fate properties of the pesticide ( aerobic soil degradation half life and linear adsorption coefficient normalized for soil organic carbon content), the maximum application rate, and existing data from 56 small scale prospective ground water monitoring studies at sites with sandy soils and shallow ground water.

Pesticide concentrations estimated by SCI GROW represent conservative or high end exposure values because the model is based on ground water monitoring studies which were conducted by applying pesticides at maximum allowed rates and frequency to vulnerable sites ( i. e., shallow aquifers, sandy, permeable soils, and substantial rainfall and/ or irrigation to maximize leaching). In most cases, a large majority of the use areas will have ground water that is less vulnerable to contamination than the areas used to derive the SCI GROW estimate. SCIGROW provides a groundwater screening exposure value to be used in determining the potential risk to human health from drinking water contaminated with the pesticide. SCIGROW estimates likely groundwater concentrations if the pesticide is used at the maximum allowable rate in areas where groundwater is exceptionally vulnerable to contamination. In most cases, a large majority of the use area will have groundwater that is less vulnerable to contamination than the areas used to derive the SCIGROW estimate. 57 APPENDIX II: Terrestrial Modeling 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 metiram on food items on Kenaga maximum and mean predicted values.

Table 1: 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 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 and others. ( 1994). 58 b. Fate v. 5.0 Model Terrestrial Exposure Values 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 *

The model calculates maximum and mean EECs based on the maximum and mean Kenaga Fletcher values listed in Table 1 above. These EECs are the maximum amounts collecting on each day during the interval chosen. The model calculates these EECs for the different food item groupings. 59 c. Fate v. 5.0 Model Sample Output for Metiram RUN No. 1 FOR Metiram ON Apples *** 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 ******* 50.000 1.000 40.000 MAXIMUM & 58 DAY AVERAGE KENAGA/ FLETCHER RESIDUES: 95th% ( mean) in ppm  SHORT BROADLEAF TALL SEED GRASS & INSECTS GRASS FRUIT ____________________ ________________ ________________ ________________ MAX3787.96( 1341.57) 2130.73( 710.24) 1736.15( 568.19) 236.75( 110.48)

Below are lists of daily Kenaga Flether pesticide residue values for four avian/ mammalian food groupings for Metiram use on Apples 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 1152.00 408.00 648.00 216.00 528.00 172.80 72.00 33.60 2 1129.41 400.00 635.29 211.76 517.65 169.41 70.59 32.94 3 1107.26 392.16 622.84 207.61 507.50 166.09 69.20 32.30 4 1085.55 384.47 610.62 203.54 497.54 162.83 67.85 31.66 5 1064.26 376.93 598.65 199.55 487.79 159.64 66.52 31.04 6 1043.39 369.54 586.91 195.64 478.22 156.51 65.21 30.43 7 1022.93 362.29 575.40 191.80 468.84 153.44 63.93 29.84 8 2154.87 763.18 1212.12 404.04 987.65 323.23 134.68 62.85 9 2112.62 748.22 1188.35 396.12 968.28 316.89 132.04 61.62 10 2071.19 733.55 1165.05 388.35 949.30 310.68 129.45 60.41 11 2030.58 719.16 1142.20 380.73 930.68 304.59 126.91 59.23 12 1990.76 705.06 1119.80 373.27 912.43 298.61 124.42 58.06 13 1951.72 691.23 1097.84 365.95 894.54 292.76 121.98 56.93 14 1913.45 677.68 1076.31 358.77 877.00 287.02 119.59 55.81 15 3027.93 1072.39 1703.21 567.74 1387.80 454.19 189.25 88.31 16 2968.55 1051.36 1669.81 556.60 1360.59 445.28 185.53 86.58 17 2910.34 1030.75 1637.07 545.69 1333.91 436.55 181.90 84.88 18 2853.27 1010.53 1604.96 534.99 1307.75 427.99 178.33 83.22 19 2797.32 990.72 1573.49 524.50 1282.10 419.60 174.83 81.59 20 2742.47 971.29 1542.64 514.21 1256.96 411.37 171.40 79.99 21 2688.69 952.24 1512.39 504.13 1232.31 403.30 168.04 78.42 22 3787.96 1341.57 2130.73 710.24 1736.15 568.19 236.75 110.48 23 3713.68 1315.26 2088.95 696.32 1702.11 557.05 232.11 108.32 24 3640.86 1289.47 2047.98 682.66 1668.73 546.13 227.55 106.19 25 3569.47 1264.19 2007.82 669.27 1636.01 535.42 223.09 104.11 26 3499.47 1239.40 1968.45 656.15 1603.92 524.92 218.72 102.07 27 3430.85 1215.09 1929.85 643.28 1572.47 514.63 214.43 100.07 28 3363.57 1191.26 1892.01 630.67 1541.64 504.54 210.22 98.10 29 3297.61 1167.90 1854.91 618.30 1511.41 494.64 206.10 96.18 30 3232.95 1145.00 1818.53 606.18 1481.77 484.94 202.06 94.29 31 3169.55 1122.55 1782.87 594.29 1452.71 475.43 198.10 92.45 32 3107.40 1100.54 1747.91 582.64 1424.23 466.11 194.21 90.63 33 3046.47 1078.96 1713.64 571.21 1396.30 456.97 190.40 88.86 60 34 2986.73 1057.80 1680.03 560.01 1368.92 448.01 186.67 87.11 35 2928.16 1037.06 1647.09 549.03 1342.07 439.22 183.01 85.40 36 2870.74 1016.72 1614.79 538.26 1315.76 430.61 179.42 83.73 37 2814.45 996.78 1583.13 527.71 1289.95 422.17 175.90 82.09 38 2759.26 977.24 1552.08 517.36 1264.66 413.89 172.45 80.48 39 2705.15 958.07 1521.65 507.22 1239.86 405.77 169.07 78.90 40 2652.10 939.29 1491.81 497.27 1215.55 397.82 165.76 77.35 41 2600.10 920.87 1462.55 487.52 1191.71 390.01 162.51 75.84 42 2549.11 902.81 1433.87 477.96 1168.34 382.37 159.32 74.35 43 2499.12 885.11 1405.76 468.59 1145.43 374.87 156.20 72.89 44 2450.12 867.75 1378.19 459.40 1122.97 367.52 153.13 71.46 45 2402.07 850.73 1351.17 450.39 1100.95 360.31 150.13 70.06 46 2354.97 834.05 1324.67 441.56 1079.36 353.25 147.19 68.69 47 2308.79 817.70 1298.69 432.90 1058.20 346.32 144.30 67.34 48 2263.52 801.66 1273.23 424.41 1037.44 339.53 141.47 66.02 49 2219.13 785.94 1248.26 416.09 1017.10 332.87 138.70 64.72 50 2175.61 770.53 1223.78 407.93 997.16 326.34 135.98 63.46 51 2132.95 755.42 1199.79 399.93 977.60 319.94 133.31 62.21 52 2091.13 740.61 1176.26 392.09 958.43 313.67 130.70 60.99 53 2050.12 726.08 1153.19 384.40 939.64 307.52 128.13 59.80 54 2009.92 711.85 1130.58 376.86 921.21 301.49 125.62 58.62 55 1970.50 697.89 1108.41 369.47 903.15 295.58 123.16 57.47 56 1931.86 684.20 1086.67 362.22 885.44 289.78 120.74 56.35 57 1893.98 670.79 1065.36 355.12 868.08 284.10 118.37 55.24 58 1856.84 657.63 1044.47 348.16 851.05 278.53 116.05 54.16 ___ _______________ _______________ _______________ _______________

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 ___ _______________ _______________ _______________ _______________

2450.95 868.04 1378.66 459.55 1123.35 367.64 153.18 71.49 61 APPENDIX III: Ecological Hazards Assessment a. Scope The toxicity testing required does not test all species of birds, fish, mammals, invertebrates, and plants. EFED uses only two surrogate species for birds ( Bobwhite quail and mallard ducks) to represent all bird species ( over 900 in the US). EFED uses three species of freshwater fish ( rainbow trout, bluegill sunfish and fathead minnow) to act as surrogate test species for all freshwater fish species ( over 900 in the US). One estuarine fish species ( sheepshead minnow) serves as surrogate for all estuarine and marine fish ( over 300 in the US). The surrogate species for terrestrial invertebrates is the honeybee. For freshwater invertebrates the surrogate species is usually the waterflea ( Daphnia magna). For estuarine and marine invertebrates the surrogate species are mysid shrimp and eastern oyster. EFED uses these four species to represent all invertbrates species ( over 10,000 in the US). For plants, there are ten surrogate species used for all terrestrial plants and five surrogate species used for all aquatic plants. There are over 20,000 plant species in the US which includes flowering plants, conifers, ferns, mosses, liverworts, hornworts and lichens. There are over 27,000 species of algae worldwide.

The surrogate species testing scheme used in this assessment assumes that a chemical's method of action and toxicity found for avian species is similar to that in all reptiles ( over 300 species in the US). The same assumption applies to amphibians ( over 200 species in the US) and fish. EFED assumes the tadpole stage of amphibians has the same sensitivity as a fish. Therefore, EFED considers the results from toxicity tests on surrogate species are applicable to other member species within their class and extrapolates this toxicity to reptiles and amphibians. EFED got the US species numbers noted in this section from: http:// www. natureserve. org/ summary ( NatureServe: An online encyclopedia of life [ web application]. 2000) and the worldwide species number from Ecological Planning and Toxicology, Inc. 1996.

b. Toxicity to Terrestrial Animals i. Birds, Acute, Subacute and Chronic EFED requires an acute oral toxicity study using the technical grade of the active ingredient ( TGAI) to find out the toxicity of metiram to birds. The avian oral LD 50 test is an acute, single dose laboratory study designed to estimate the quantity of toxicant needed to cause 50% mortality in a test population of birds. The preferred test species is either the mallard duck, a waterfowl, or Bobwhite quail, an upland game bird. Adult birds receive the TGAI by oral intubation with results expressed as LD 50 in milligrams ( mg) active ingredient ( a. i.) per kilogram ( kg). Toxicity category descriptions are the following ( Brooks, 1973):

If the LD50 is less than 10 mg a. i./ kg, then the test substance is very highly toxic. If the LD50 is 10 to 50 mg a. i./ kg, then the test substance is highly toxic. If the LD50 is 51 to 500 mg a. i./ kg, then the test substance is moderately toxic. If the LD50 is 501 to 2,000 mg a. i./ kg, then the test substance is slightly toxic. 62 If the LD50 is greater than 2,000 mg a. i./ kg, then the test substance is practically nontoxic.

Based on the study listed in Table 1, metiram, taken orally, is practically nontoxic to birds. MRID No. 40656901 fulfills guideline 71 1( a).

Table 1: Avian ( also Reptilian and Terrestrial Phase Amphibian) Acute Oral Toxicity  Metiram Technical Species % ai LD 50 ( mg ai/ kg) Toxicity Category MRID No. Author/ year Classification1 Northern bobwhite ( Colinus virginianus) 95 > 2150 practically nontoxic 40656901/ Fletcher, D./ 1988 Core 1 Core ( study satisfies guideline). Supplemental ( study is scientifically sound, but does not satisfy guideline)

EFED requires two dietary studies using the TGAI to find out the toxicity of metiram to birds. These avian dietary LC 50 tests, using the Mallard Duck and Bobwhite Quail, are acute, eight day dietary laboratory studies designed to estimate the quantities of toxicant needed to cause 50% mortality in the two respective test populations of birds. Juvenile birds received the TGAI mixed in their diet for five days followed by three days of " clean" diet. The results, expressed as LC 50 , is in parts per million ( ppm) active ingredient ( a. i.) of the diet. Toxicity category descriptions are the following ( Brooks, 1973):

If the LC50 is less than 50 ppm a. i., then the test substance is very highly toxic. If the LC50 is 50 to 500 ppm a. i., then the test substance is highly toxic. If the LC50 is 501 to 1,000 ppm a. i., then the test substance is moderately toxic. If the LC50 is 1001 to 5,000 ppm a. i., then the test substance is slightly toxic. If the LC50 is greater than 5,000 ppm a. i., then the test substance is practically nontoxic.

Taken orally, metiram mixed in the diet, is slightly toxic to birds ( see Table 2). MRID Nos. 00108004 and 00108005 have fulfilled guidelines 71 2( a and b). EFED will use the toxicity value ( LC 50 ) appearing in the shaded area of the table to calculate the acute avian risk quotients ( RQs).

Table 2: Avian ( also Reptilian and Terrestrial Phase Amphibian) Subacute Dietary Toxicity  Metiram Technical Species % ai LC50( ppm ai) Toxicity Category MRID/ Accession ( AC) No. Author/ Year Study Classification Mallard Duck ( Anas platyrhynchos) 80 > 3712 slightly toxic 00108005// Fink, R./ 1974 Core Northern Bobwhite Quail ( Colinus virginianus) 80 37121 slope not determined slightly toxic 00108004/ Fink, R./ 1974 Core 1 Only highest dose showed percent mortality ( 50%), therefore the LC50 determined is not statistically sound.

EFED requires avian reproduction studies using the Bobwhite Quail and Mallard Duck to estimate the quantity of toxicant needed to adversely affect reproduction in a test population of birds. Breeding birds receive the TGAI mixed in their diet throughout their breeding cycle. Test birds are 63 approaching their first breeding season and are 18 to 23 weeks old. The onset of the exposure period is at least 10 weeks before egg laying. The exposure period during egg laying is 10 weeks with a withdrawal period of three added weeks if the observer notes a decrease in egg laying. The No Observed Adverse Effect Concentration ( NOAEC) and various observable effect levels, expressed as the Lowest Observable Adverse Effect Concentration ( LOAEC) are the results determined from these studies. These results are in parts per million of active ingredient ( ppm a. i.) in the diet.

EFED requires avian reproduction studies for metiram because birds may be subject to repeated or continuous exposure to the pesticide, especially preceding or during the breeding season. In addition, the pesticide is stable in the environment and potentially toxic amounts may persist in animal feed. Finally, information gathered from mammalian reproduction studies shows metiram's use may adversely affect reproduction in terrestrial vertebrates. The preferred test species are mallard duck and bobwhite quail. Table 3 shows the results of these tests. EFED will use the toxicity value ( NOAEC) appearing in the shaded area of the table to calculate the chronic avian risk quotients ( RQs).

MRID No. 42539102, in Table 3, showed chronic toxic effects in mallard ducks. These effects included: reduced egg production; reduced mean egg weight; reduced fertility rate; reduced number of hatched ducklings; reduced number of 14 day old survivors; and an increased rate of early embryonic deaths. The reproduction NOAEC and LOAEC were 50 and 300 ppm, respectively. MRID No. 42539102 fulfills guideline 71 4( b).

EFED classified a bobwhite quail reproduction study ( MRID No. 41082001) supplemental because of high mortality and a high number of cracked eggs ( that is, greater than 18%) in the control group. This study showed an NOAEC greater than 500 ppm ( the highest dose tested). In a 3 26 96 memorandum from A. Maciorowski ( EFED) to W. Waldrop ( SRRD), EFED made the following decision about the need for a core bobwhite quail reproductive study:

" Core mallard reproduction studies exist for metiram, mancozeb, and maneb... Collectively, these studies indicate that the mallard is more sensitive than the bobwhite quail to the EBDCs. Therefore, additional bobwhite quail reproduction testing with metiram is not required..."

Mallard duck reproduction NOAECs for mancozeb and maneb are 10 ppm and 20 ppm, respectively. Bobwhite quail NOAECs are 125 to 300 ppm for mancozeb and > 500 ppm for maneb. 64 Table 3: Avian ( Reptilian & Terrestrial Phase Amphibian) Reproduction Chronic Toxicity  Metiram Technical Species/ Study Duration % ai NOAEC/ LOAEC ( ppm ai) LOAEC Endpoints MRID No. Author/ year Classification1 Northern bobwhite ( Colinus virginianus) / 22 weeks 93 > 500/ not determined Not applicable 41082001/ Fletcher, D.& C. Pedesen/ 1989 Supplemental Mallard Duck ( Anas platyrhynchos) / 22 weeks 97 50/ 300 Reduced egg production; reduced mean egg weight; reduced fertility rate; reduced number of hatched ducklings; reduced number of 14 day old survivors; and an increased rate of early embryonic deaths. 42539102/ Munk, R./ 1992 Core 1 Core ( study satisfies guideline). Supplemental ( study is scientifically sound, but does not satisfy guideline)

ii. Mammals, Acute and Chronic 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, the metiram toxicological chapter dated 1/ 6/ 00 ( D249581), the final Hazard Identification Assessment Review Committee ( HIARC) report on metiram dated November 15, 1999 ( HED document number 013838), and a draft revised endpoint selection table from a 9/ 18/ 01 HIARC meeting. 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 LD50 is less than 10 mg a. i./ kg, then the test substance is very highly toxic. If the LD50 is 10 to 50 mg a. i./ kg, then the test substance is highly toxic. If the LD50 is 51 to 500 mg a. i./ kg, then the test substance is moderately toxic. If the LD50 is 501 to 2,000 mg a. i./ kg, then the test substance is slightly toxic. If the LD50 is greater than 2,000 mg a. i./ kg, then the test substance is practically nontoxic.

The results show that metiram is practically nontoxic to mammals from acute oral exposure ( Table 4).

Table 4: Mammalian Acute Oral Toxicity  Metiram Species % ai LD50 ( mg ai/ kg) Toxicity Category) Affected Endpoints MRID or Accession ( AC) No.

Technical laboratory rat ( Rattus norvegicus) technical > 10,000 ( male) 8,000 ( female) practically nontoxic mortality 009768 laboratory rat ( Rattus norvegicus) 80 > 5,000 ( male & female) practically nontoxic mortality 009926 65 1. Acute Dermal and Inhalation Toxicity Testing As well as acute oral routes of exposure, terrestrial vertebrates entering a treatment area may also receive dermal and inhalation exposure to metiram. Toxicity category descriptions associated with dermal routes of exposure include ( US EPA CFR. Part 156):

If the LD50 is less than or equal to 200 mg/ kg, then the test substance is in Toxicity Category I. If the LD50 is greater than 200 through 2,000 mg/ kg, then the test substance is in Toxicity Category II. If the LD50 is greater than 2,000 through 5,000 mg/ kg, then the test substance is in Toxicity Category III If the LD50 is greater than 5,000 mg/ kg, then the test substance is in Toxicity Category IV.

The results show that metiram is a Category III toxicant to mammals from dermal exposure ( Table 5).

Table 5: Mammalian Acute Dermal Toxicity  Metiram Technical Surrogate Species % ai LD50 ( mg ai/ kg) Toxicity Category Affected Endpoints MRID or Accession ( AC) No.

laboratory rat ( Rattus norvegicus) 97.6 > 2,000 Category III mortality 009768 Table 6 shows metiram's acute inhalation toxicity results. Toxicity category descriptions associated with inhalation routes of exposure include ( US EPA CFR. Part 156):

If the LC50 is less than or equal to 0.05 mg/ liter, then the test substance is in Toxicity Category I. If the LC50 is greater than 0.05 mg/ liter through 0.5 mg/ liter, then the test substance is in Toxicity Category II. If the LC50 is greater than 0.5 mg/ liter through 2.0 mg/ liter, then the test substance is in Toxicity Category III If the LC50 is greater than 2.0 mg/ liter, then the test substance is in Toxicity Category IV.

Metiram is a Category IV toxicant to mammals based on acute inhalation exposure.

Table 6: Mammalian Acute Inhalation Toxicity  Metiram Technical Surrogate Species/ Formulation % A. I. LC50 ( mg/ liter) Toxicity Category Affected Endpoints MRID or Accession ( AC) No.

laboratory rat ( Rattus norvegicus) technical > 5.7 Category IV mortality 009768 2. Mammalian Sub chronic Toxicity Testing 66 Table 7 shows the filed mammalian subchronic feeding studies in rats. These studies show results from extended exposure ( that is, 3 month feeding studies). The result show metiram residues in the diet at levels of 80 ppm will cause reduced forelimb strength in female rats. Levels of 1,000 ppm, in mice, will decrease total serum, thyroxine ( T 4 , a thyroid hormone) concentration in both sexes.

Table 7: Mammalian Sub chronic Toxicity  Metiram Surrogate Species/ % ai NOAEL/ LOAEL ( ppm) LOAEL Endpoints MRID or Accession ( AC) No.

Laboratory rat ( Rattus norvegicus)/ feeding 3 months 94.8 5.0/ 80.0 Reduced forelimb strength in females. 42539101 Laboratory mouse ( Mus musculus)/ feeding 3 months 95.0 300/ 1,000 Decrease in total serum, thyroxine ( T 4 , a thyroid hormone) concentration in both sexes. 42595001 3. Mammalian Reproductive and Developmental Toxicity Testing Table 8 shows treatment related developmental effects caused by metiram. The developmental effects in rats include increased pre and post implantation losses, decreased litter size, and decreased litter weight at an exposure of 1,600 ppm ( LOAEL) ( AC No. 242188). This same study showed maternal decreases in body weight gains at an exposure of 3,200 ppm ( LOAEL). A metiram developmental study, using rabbits as the test species, showed an increased incidence of abortions at a 1,320 ppm ( LOAEL) exposure level. However, because of inadequate examination of the aborted fetuses, this study showed no developmental defects ( MRID No. 40711401). A 3 generational reproductive study with metiram, using rats as the test species, indicated there was a maternal decrease in body weight during gestation and lactation of the treatment groups, as compared to the controls, at exposure levels of 320 ppm ( LOAEL). At this same level ( 320 ppm) reproductive toxicity was noted based on decreased mating performance ( increased precoital time) in the F2 generation ( two generations removed from the original parent generation). There were no direct adverse effects noted in the offspring ( no dose related effect on litter sizes, no significant cumulative losses in any gerneration, no adverse body weight changes and no histological findings attributed to treatment) of this reproductive study at the highest dose tested ( 320 ppm) ( AC No. 247214).

Table 8: Mammalian Developmental and Reproductive Chronic Toxicity  Metiram Technical Species/ Study Duration % ai Test Type NOAEL/ LOAEL Toxicity Value ( mg/ kg/ day) Affected Endpoints MRID or Accession ( AC) No.

laboratory rat ( Rattus norvegicus)/ from gestation day 6 through gestation day 15 96.8 Developmental 80/ 160 ( 1600/ 3200 ppm) 1 ( maternal) 80/ 160 ( 800/ 1600ppm) 1 ( developmental) mat.  decreased body weight gain dev.  increased pre and postimplantation losses, decreased litter size, and decreased litter weight 242188 Table 8: Mammalian Developmental and Reproductive Chronic Toxicity  Metiram Technical Species/ Study Duration % ai Test Type NOAEL/ LOAEL Toxicity Value ( mg/ kg/ day) Affected Endpoints MRID or Accession ( AC) No.

67 laboratory rabbit ( Sylvivlagus sp.)/ from gestation day 7 through gestation day 19 97.9 Developmental 10/ 40 ( 330/ 1320 ppm) 1 ( maternal) not determined ( developmental) mat.  abortions dev.  not determined 40711401 laboratory rat ( Rattus norvegicus)/ 3 generation 96.8 Reproductive 2.2/ 19.8 ( 40/ 320 ppm) 2 females ( parental) 1.8( m) 2.2( f)/ 14.2( m) 19.9( f) ( 40/ 320 ppm) 2 14.2( m) 19.8( f)/ not applicable ( 320/ not applicable) 2 ( reproductive) parental  decreased body weight during gestation & lactation for females reproductive  decreased mating performance in the F2 generation offspring  no adverse effects were observed at the highest dose tested 247214 1 ppm conversion based on: 1 mg/ kg/ day = 20 ppm in adult rats, 10 ppm in younger rats, and 33 ppm in rabbits. ( Nelson, 1975) 2 ppm value provided in study review iii. Insect Acute Contact A honey bee acute contact study using the TGAI is required for metiram because its outdoor use will result in honey bee exposure. The acute contact LD 50 , using the honey bee, Apis mellifera, is an acute contact, single dose laboratory study designed to estimate the quantity of toxicant required to cause 50% mortality in a test population of bees. The TGAI is administered by one of two methods: whole body exposure to technical pesticide in a nontoxic dust diluent; or, topical exposure to technical pesticide via micro applicator. The median lethal dose ( LD 50 ) is expressed in micrograms of active ingredient per bee (: g a. i./ bee). Results of this test are tabulated below ( Table 9). Toxicity category descriptions are the following ( Atkins, 1981):

If the LD50 is less than 2 : g a. i./ bee, then the test substance is highly toxic. If the LD50 is 2 to less than 11 : g a. i./ bee, then the test substance is moderately toxic. If the LD50 is 11 : g a. i./ bee or greater, then the test substance is practically nontoxic The LD 50 for metiram was 437 µ g per bee which categorizes metiram as practically nontoxic to bees. The guideline ( 141 1) is fulfilled ( MRID No. 00066220).

Table 9: Non target Insect Acute Contact Toxicity  Metiram Species % ai LD50 ( µ g a. i./ bee) Toxicity Category MRID/ Accession ( AC) No. Author/ Year Study Classification1 Honey bee ( Apis mellifera) 80 437 practically nontoxic 00066220/ Atkins, E. et al./ 1977 Core 1 Core ( study satisfies guideline). Supplemental ( study is scientifically sound, but does not satisfy guideline) 68 iv. Insect Residual Contact A honey bee toxicity of residues on foliage study is required on an end use product for any pesticide intended for outdoor application when the proposed use pattern indicates that honey bees may be exposed to the pesticide and when the formulation contains one or more active ingredients having an acute contact honey bee LD 50 which falls in the moderately toxic or highly toxic range. The purpose of this guideline study is to develop data on the residual toxicity to honey bees. Bee mortality determinations are made from bees exposed to treated foliage harvested at various time periods after treatment. Metiram, as indicated in the acute toxicity test in Table 9, above, is practically nontoxic to honey bees. Because of this, a honey bee toxicity of residues on foliage ( guideline 141 2) is not required for metiram.

v. Terrestrial Field Testing No studies were submitted and no studies are required c. Aquatic Organism Toxicity i. Toxicity to Freshwater Animals 1. Freshwater Fish, Acute Two freshwater fish toxicity studies using the TGAI are required to establish the toxicity of metiram to fish. The preferred test species are rainbow trout ( a coldwater fish, Guideline 72 1c) and bluegill sunfish ( a warmwater fish; Guideline 72 1a). Results of these tests are tabulated below. The toxicity category descriptions for freshwater and estuarine/ marine fish and aquatic invertebrates, are defined below in parts per million ( ppm), the standard units of measure. The toxicity category descriptions for freshwater and estuarine/ marine fish and aquatic invertebrates, are defined below in parts per million ( ppm), the standard units of measure ( Brooks, 1973). The toxicity values ( LC 50 ) appearing in the shaded area of the tables will be used to calculate the acute aquatic risk quotients ( RQ's) in subsequent sections.

If the LC50 is less than 0.1 ppm a. i., then the test substance is very highly toxic. If the LC50 is 0.1 to 1.0 ppm a. i., then the test substance is highly toxic. If the LC50 is greater than 1 and up through 10 ppm a. i., then the test substance is moderately toxic. If the LC50 is greater than 10 and up through 100 ppm a. i., then the test substance is slightly toxic. If the LC50 is greater than 100 ppm a. i., then the test substance is practically nontoxic.

Metiram is highly toxic to coldwater freshwater fish on an acute basis ( rainbow trout LC 50 = 0.23 ppm based on measured, filtered samples) ( see Table 10 below). The guideline ( 72 1c) is fulfilled ( MRID 43525001). There are numerous studies classified invalid because test concentrations were not measured; as is required for poorly soluble compounds [ e. g., bluegill LC 50 > 160 ppm ( MRID 40945501); bluegill LC 50 < 42 and > 26 ppm ( MRID 44224401); and rainbow trout LC 50 of 46.7 ppm ( 40497011). The freshwater fish acute toxicity guideline requirement for a a warmwater fish ( Guideline 72 1a) has not been fulfilled and a Core study is required to be submitted. 69 An outdoor, multiple application ( 4 applications every 7 days) study exposed juvenile ( 3 months old) rainbow trout to metiram ( MRID No. 45933402). The trout were exposed under static conditions while contained in 0.55 cu. meter stainless steel basins. The test basins contained ~ 2 cm. of natural lake sediment in the bottom. The 28 day nominal LC 50 based on mortality was 0.276 ppm ai. A chronic NOAEC of 0.07 ppm ai based on weight loss and reduced growth were also determined in this study. This study was determined to be scientifically sound and categorized as supplemental because the study did not fulfill any guideline study requirement.

Table 10: Freshwater Fish 96 hr Acute Toxicity  Metiram Technical Species/ Flow through or Static/ Duration % ai LC 50 / ( ppm ai)/ ( measured/ nominal) Toxicity Category MRID / Accession No./ Author/ Year Study Classification1 Rainbow Trout ( Salmo gairdneri)/ flowthrough 96 hour 71.04 0.23 ( measured) Slope = 2.23 highly toxic 43525001/ Monk, R./ 1994 Core Rainbow Trout ( Oncorhynchus mykiss)/ static/ 28 day 68.5 0.276 ( nominal) highly toxic 45933402/ Junker, M./ 2002 Supplemental 1 Core ( study satisfies guideline). Supplemental ( study is scientifically sound, but does not satisfy guideline)

2. Freshwater Fish, Chronic A freshwater fish early life stage test using the TGAI is required for metiram because the end use product is expected to be transported to water from the intended use site, and the following conditions are met: ( 1) the pesticide is intended for use such that its presence in water is likely to be continuous or recurrent, ( 2) an aquatic acute LC 50 or EC 50 is less than 1ppm, and ( 3) the EEC in water is equal to or greater than 0.01 of any acute LC 50 or EC 50 value. Acceptable freshwater test species are rainbow trout, brook trout, coho salmon, Chinook, bluegill, brown trout, lake trout, northern pike, fathead minnow, white sucker and channel catfish. The fish early life stage is a laboratory test designed to estimate the quantity of toxicant required to adversely effect the reproductive capabilities of a test population of fish. The test should be performed using flowthrough conditions. The TGAI is administered into water containing the test species, providing exposure throughout a critical life stage, and the results are expressed as a No Observed Adverse Effect Concentration ( NOAEC) and LOAEC ( Lowest Observed Adverse Effect Concentration) in parts per billion ( ppb) of active ingredient. The No Observed Adverse Effect Concentration represents an exposure concentration, at or below which biologically significant effects will not occur to species of similar sensitivities. A rainbow trout early life stage study submitted with a reported NOAEC of 31.6 ppb ( MRID No. 43770401) was categorized as invalid due to study design flaws. The EFED does not have a study to fulfill this required freshwater fish early life stage test ( Guideline 72 4a) for metiram. A guideline study is required to be submitted.

A freshwater fish early life cycle test ( Guideline 72 5) using the TGAI of metiram is held in reserve pending the results of the required freshwater fish early life stage test ( Guideline 72 4a) for metiram mentioned above.

3. Freshwater Invertebrates, Acute A freshwater aquatic invertebrate toxicity test using the TGAI is required to establish the acute toxicity of metiram to aquatic invertebrates. The preferred test organism is Daphnia magna, but early 70 instar amphipods, stoneflies, mayflies, or midges may also be used. A supplemental acute daphnid study ( MRID No. 44301101) indicates metiram's freshwater aquatic invertebrates EC 50 value is greater than 0.358 ppm based on measured, unfiltered samples. The study was classified supplemental because an EC 50 was not established, and because samples were not filtered prior to analytical measurement. Results of this test are tabulated below ( Table 11). Guideline 72 2( a) for the TGAI of metiram is not fulfilled. A core study to fulfill this guideline is required.

There was one acute toxicity daphnid study classified invalid because test concentrations were not measured ( MRID No. 40497003) as is required for poorly soluble compounds and another daphnid acute toxicity study ( MRID No. 43525002) also categorized as invalid because of study design flaws.

Table 11: 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.) 70 > 0.358 ( measured unfiltered) Slope = not applicable highly toxic 44301101/ Maisch/ 1997 Supplemental 1 Core ( study satisfies guideline). Supplemental ( study is scientifically sound, but does not satisfy guideline)

4. Freshwater Invertebrate, Chronic A freshwater aquatic invertebrate life cycle test using the TGAI is required for metiram since the enduse product is expected to be transported to water from the intended use site, and the following conditions are met: ( 1) the pesticide is intended for use such that its presence in water is likely to be continuous or recurrent, ( 2) the aquatic acute LC 50 or EC 50 is less than 1.0 ppm, and ( 3) the EEC in water is equal to or greater than 0.01 of any acute EC 50 or LC 50 value. The preferred test species is Daphnia magna. Daphnid life cycle tests ( MRID Nos. 43770402 and 44301102 ) were submitted to fulfill this guideline requirement but were classified as invalid due to study design flaws. A core freshwater aquatic invertebrate life cycle test using the TGAI is required to be submitted for metiram. Guideline 72 4( b) for metiram is not fulfilled.

5. Freshwater Whole Sediment Toxicity Invertebrates, Acute Whole Sediment Acute Toxicity ( Guideline 850.1735) testing using the TGAI is required to determine the toxicity and bioaccumulation potential of chemicals in sediments in benthic organisms. This test is a 28 day study and the preferred test species are the amphipod, Hyalella azteca and the midge, Chironomus tentans. Natural sediment is spiked with different concentrations of test chemical and the results from the sediment toxicity tests can be used to determine causal relationships between the chemical and biological response. Reported endpoints from whole sediment toxicity tests may include the LC 50 or EC 50 , NOAEC, or the LOAEC. Whole Sediment Acute Toxicity Invertebrates, Freshwater ( Guideline 850.1735) testing is required for metiram because metiram is toxic to aquatic invertebrates, persistent in the environment, and binds to sediment. This guideline has not been fulfilled and a guideline study is required to be submitted. 71 6. Freshwater Field Studies No studies were submitted and no studies are required.

ii. Toxicity to Estuarine and Marine Animals 1. Estuarine and Marine Fish, Acute Acute toxicity testing with estuarine and marine fish using the TGAI is required for metiram because the end use product is expected to reach the marine/ estuarine environment because of its use in coastal counties. The preferred test organism is the sheepshead minnow. The EFED does not have an estuarine/ marine fish acute toxicity test to fulfill this guideline requirement for metiram. A core study for acute toxicity testing of TGAI metiram on estuarine/ marine fish ( Guideline 72 3a) is required to be submitted.

2. Estuarine and Marine Fish, Chronic An estuarine/ marine fish early life stage toxicity test using the TGAI is required when the end use product is expected to be transported to the estuarine/ marine environment from the intended use site, and the following conditions are met: the pesticide is intended for use such that its presence in water is likely to be continuous or recurrent and the EEC in water is equal to or greater than 0.01 of any acute LC 50 or EC 50 value. The preferred test species is sheepshead minnow. The guideline ( 72 4a) estuaine/ marine fish is not fulfilled for metiram. An early life stage test using the TGAI ( Guideline 72 4a) for metiram is held in reserve pending the results of the required acute toxicity testing ( Guideline 72 3a) for metiram mentioned above.

3. Estuarine and Marine Invertebrates, Acute Acute toxicity testing with estuarine/ marine invertebrates using the TGAI is required for metiram because the end use product is expected to reach the marine/ estuarine environment because of it use in coastal counties. The preferred test species are mysid shrimp and eastern oyster. The EFED does not have an estuarine/ marine invertebrate acute toxicity tests to fulfill this guideline requirement for metiram. Core studies for acute toxicity testing of TGAI metiram on estuarine/ marine invertebrates ( Guidelines 72 3b & c) are required to be submitted.

4. Estuarine and Marine Invertebrate, Chronic An estuarine/ marine invertebrate life cycle toxicity test ( Guideline 72 4b) using the TGAI is required when the end use product is expected to be transported to the estuarine/ marine environment from the intended use site, the pesticide is intended for use such that its presence in water is likely to be continuous or recurrent, any aquatic acute LC 50 or EC 50 is less than 1.0 ppm, and the EEC in water 72 is equal to or greater than 0.01 of any acute LC 50 or EC 50 value. The preferred test species is mysid shrimp. An estuarine/ marine invertebrate life cycle toxicity test ( Guideline 72 4b) for metiram is held in reserve pending the results of the required acute toxicity testing ( Guidelines 72 3b & c) for metiram mentioned above.

5. Estuarine and Marine Whole Sediment Toxicity Invertebrates, Acute Whole sediment toxicity testing with estuarine/ marine invertebrates using the TGAI is being required for metiram because metiram has a high affinity for sediment and the end use product is expected to reach the marine/ estuarine environment because of it use in coastal counties. This test lasts 10 or more days and the preferred test species are four species of estuarine/ marine amphipods; Ampelisca abdita, Eohaustorius estuarius, Rhepoxynius abronius, and Leptocheirus plumulosus. The EFED does not have an estuarine/ marine invertebrate whole sediment toxicity tests to fulfill this guideline requirement for metiram. A core study for Whole Sediment Acute Toxicity Invertebrates, Marine ( Guideline 850.1740) testing of TGAI metiram on estuarine/ marine invertebrates is required to be submitted.

6. Estuarine and Marine Field Studies No studies were submitted and no studies are required.

iii. Toxicity to Plants 1. Terrestrial Plants Terrestrial plant Tier I seedling emergence and vegetative vigor testing of a metiram TEP is currently recommended for all pesticides having outdoor uses. For seedling emergence and vegetative vigor testing the following plant species and groups should be tested: ( 1) six species of at least four dicotyledonous families, one species of which is soybean ( Glycine max) and the second is a root crop, and ( 2) four species of at least two monocotyledonous families, one of which is corn ( Zea mays). Tier I tests measure the response of plants, relative to a control, at a test level that is equal to the highest use rate ( expressed as lbs ai/ A). Tier II studies are required if the Tier I studies indicate any of the test species, when exposed to the test material, displayed a $ 25% inhibition of various growth parameters as compared to the control.

Tier I seedling emergence [ guideline 122 1( a)] and vegetative vigor [ guideline 122 1( b)] studies for the metiram have not be received and submission of these studies for review by the EFED are recommended. The submission recommendation for Tier II seedling emergence [ guideline 123 1( a)] and vegetative vigor [ guideline 123 1( b)] testing for the metiram is being held in reserve pending the results of Tier I testing.

2. Aquatic Plants Aquatic plant testing is recommended for all pesticides having outdoor uses ( Keehner. July 1999). The tests are performed on species from a cross section of the non target aquatic plant population. 73 The preferred test species are duckweed ( Lemna gibba), marine diatom ( Skeletonema costatum), blue green algae ( Anabaena flos aquae), freshwater green alga ( Selenastrum capricornutum), and a freshwater diatom. Tier I aquatic plant testing is a maximum dose test designed to quickly evaluate the toxic effects to the test species in terms of growth and reproduction and to determine the need for additional 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 being tested at the Tier I level. Tier II testing is aimed to determine the detrimental effect levels of the chemical on the aquatic plants which showed a greater than 50% detrimental effect in Tier I testing.

For metiram, one Tier II supplemental study has been submitted for Ankistrodesmus bibraianus, a freshwater green alga. Results of Tier II toxicity testing on the technical material are tabulated in Table 12, below. The EC 50 for Ankistrodesmus bibraianus was 77.0 ppb a. i. based on nominal concentrations; the NOAEC was 13.0 ppb. This study was classified as supplemental principally because inappropriate cell inoculum levels were used, the concentrations used were not measured, and the lighting regime was inappropriate. The toxicity value ( EC 50 ) appearing in the shaded area of the table will be used to calculate the acute risk quotients ( RQ's) in subsequent sections. Guideline 123 2 ( Tier II) has been not been fulfilled. Core Tier I or Tier II aquatic plant growth testing need to be submitted for duckweed ( Lemna gibba), marine diatom ( Skeletonema costatum), blue green algae ( Anabaena flos aquae), freshwater green alga ( Selenastrum capricornutum), and a freshwater diatom.

Table 12: Non target Aquatic Plant Toxicity ( Tier II)  Metiram Species/ duration % A. I. EC50/ NOAEC ( ppb ai) MRID No. Author/ year Classification1 Nonvascular Plants freshwater green algae ( Ankistrodesmus bibraianus) / 72 hrs. 80 77.0/ 13.0 ( nominal) Slope = 1.65 43199601/ Dohmen, G./ 1990 Supplemental 1 Core ( study satisfies guideline). Supplemental ( study is scientifically sound, but does not satisfy guideline).

3. Aquatic Plant Field Studies No studies were submitted and no studies are required. 74 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 non target 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 non target 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 non target 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 non target 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 has 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 non probabilistic and have numerical and dichotomous results. The numerical result 75 drawn from the calculation either exceeds a fixed LOC or does not exceed it. ( US EPA. June 30, 1995).

Table 1. Risk presumptions for terrestrial animals based on risk quotients ( RQ) and levels of concern ( LOC).

Risk Presumption RQ LOC Birds Acute High 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/ NOEC 1 Wild Mammals Acute High 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/ NOEC 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 High 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/ or NOEC 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 High Risk EEC1/ EC 25 1 Acute Endangered Species EEC/ EC 05 or NOEC 1 Aquatic Plants Acute High Risk EEC2/ EC 50 1 Acute Endangered Species EEC/ EC 05 or NOEC 1 1 EEC = lbs ai/ A 2 EEC = ( ppb/ ppm) in water 76 b. Exposure and Risk to Terrestrial Animals i. Birds Metiram's acute dietary RQs exceed acute, acute restricted use and acute endangered species LOCs for tobacco, apple, and potato uses. The RQs range from 0.56 to 1.22 ( see Table 4, below). Acute endangered species levels of concern ( LOCs) are exceeded for all metiram use patterns at maximum EEC levels ( RQ range from 0.11 to 1.22 for a 35 day metiram half life value estimate). The chronic risk quotients for multiple broadcast applications of nongranular metiram products are also tabulated below in Table 4. The results indicate, for multiple applications of metiram, the avian chronic LOCs are exceeded for all uses patterns. RQs exceed chronic LOCs ranging from a high of 91 from the tobacco use to a low of 1 from metiram's uses on potatoes and ornamental nonflowering plants. 77 Table 4: Avian Acute and Chronic Risk Quotients for Multiple Broadcast Applications of Nongranular Metiram based on a Bobwhite Quail ( Colinus virginianus) LC50 of 3,712 ppm and a Mallard Duck ( Anas platyrhynchos) NOAEC of 50 ppm a . Application Rate Chronic RQ Chronic RQ Acute RQ Acute RQ ( lbs ai/ A)/

Based on Based on Based on Based on Number of Mean EECs Maximum EECs Mean EECs Maximum EECs Mean Maximum Applications/ Site/

( Mean EEC/ NOAEC) 3 ( Max. EEC/ NOAEC) 3 ( Mean EEC/ LC50) 2 ( Max. EEC/ LC50) 2 EEC ( ppm) 1 EEC ( ppm) 1 Food Items Interval Application Method 27 76 0.36 1.02 1,342 3,788 Short grass 4.8/ 4 Apples 11 35 0.15 0.47 568 1,736 Tall grass 7 day interval ground & aerial 14 43 0.19 0.57 710 2,131 Broadleaf plants/ Insects 2 5 0.03 0.06 110 237 Seeds 14 41 0.19 0.55 721 2,037 Short grass 1.6/ 7 Potatoes 6 19 0.08 0.25 305 933 Tall grass 5 day interval ground & aerial 8 23 0.10 0.31 382 1,146 Broadleaf plants/ Insects 1 3 0.02 0.03 59 127 Seeds 32 91 0.43 1.22 1,605 4,533 Short grass 6.8/ 3b Tobacco 14 42 0.18 0.56 680 2,077 Tall grass 4 day interval ground 17 51 0.23 0.69 850 2,550 Broadleaf plants/ Insects 3 6 0.04 0.08 132 283 Seeds 7 20 0.10 0.27 357 1,009 Short grass 1.6/ 3b Ornamental 3 9 0.04 0.12 151 463 Tall grass 7 day interval ( nonflowering plants)

4 11 0.05 0.15 189 568 Broadleaf plants/ Insects ground 0.6 1 0.01 0.02 29 63 Seeds 5 15 0.07 0.20 268 757 Short grass 1.2/ 3b Ornamental 2 7 0.03 0.09 114 347 Tall grass 7 day interval ( woody shrubs & vines)

3 9 0.04 0.11 142 426 Broadleaf plants/ Insects ground 0.4 0.9 0.006 0.01 22 47 Seeds 1 Assumes degradation using FATE version 5.0 program with a half life of 35 days. EFED uses this value as a default value when the foliar dissipation for a particular pesticide is unknown.

2 RQ greater or equal to 0.5 exceeds acute, acute restricted use and acute endangered species LOCs.

RQ greater or equal to 0.2 exceeds acute restricted use and acute endangered species LOCs.

RQ greater or equal to 0.1 exceeds acute endangered species LOCs. 3 RQ greater or equal to 1.00 exceeds chronic LOC.

a Due to reduced egg production, reduced mean egg weight, reduced fertility rate,

reduced number of hatched ducklings, reduced number of 14 day old survivors,

and an increased rate of early embryonic deaths. b Maximum number of applications/ year or crop cycle not specified ( assumed 3 applications). 78 The 35 day foliar dissipation half life used in calculating RQs in Table 4 represents an uncertainty. Metiram's total foliar dissipation half life is unknown. For comparative purposes, EFED is providing an estimate of metiram's risk to birds based on lessened half life value. Table 4a shows modeling using a 3 day foliar dissipation half life for metiram. Assuming a 3 day foliar dissipation half life acute, acute restricted use and acute endangered species LOCs are exceeded for only the tobacco use ( RQ = 0.68 for short grass). The acute endangered species LOC are still exceeded for all metiram's uses ( RQ range from 0.1 to 0.68) with most uses exceeded for birds feeding on shortgrass only. Assuming a 3 day foliar dissipation half life, the avian chronic RQs are still exceeding the LOC for all metiram's uses. RQs exceed chronic LOCs ranging from a high of 50.7 from the tobacco use to a low of 1.8 from metiram's uses on apples. 79 Table 4a: Avian Acute and Chronic Risk Quotients for Multiple Broadcast Applications of Nongranular Metiram based on a Bobwhite Quail ( Colinus virginianus ) LC50 of 3,712 ppm and a Mallard Duck ( Anas platyrhynchos ) NOAEC of 50 ppma . Application Rate Chronic RQ Chronic RQ Acute RQ Acute RQ ( lbs ai/ A)/

Based on Based on Based on Based on Number of Mean EECs Maximum EECs Mean EECs Maximum EECs Mean Maximum Applications/ Site/

( Mean EEC/ NOAEC) 3 ( Max. EEC/ NOAEC) 3 ( Mean EEC/ LC50) 2 ( Max. EEC/ LC50) 2 EEC ( ppm) 1 EEC ( ppm) 1 Food Items Interval Application Method 10.2 28.7 0.14 0.39 508 1,435 Short grass 4.8/ 4 Apples 4.3 13.2 0.06 0.18 215 658 Tall grass 7 day interval ground & aerial 5.4 16.1 0.07 0.22 269 807 Broadleaf plants/ Insect 0.8 1.8 0.01 0.02 42 90 Seeds 4.0 11.2 0.05 0.15 198 560 Short grass 1.6/ 7 Potatoes 1.7 5.1 0.02 0.07 84 257 Tall grass 5 day interval ground & aerial 2.1 6.3 0.03 0.08 105 315 Broadleaf plants/ Insect 0.3 0.7 0.00 0.01 16 35 Seeds 18.0 50.7 0.24 0.68 898 2,537 Short grass 6.8/ 3b Tobacco 7.6 23.3 0.10 0.31 381 1,163 Tall grass 4 day interval ground 9.5 28.5 0.13 0.38 476 1,427 Broadleaf plants/ Insect 1.5 3.2 0.02 0.04 74 159 Seeds 3.4 9.5 0.05 0.13 168 475 Short grass 1.6/ 3b Ornamental 1.4 4.4 0.02 0.06 71 218 Tall grass 7 day interval ( nonflowering plants)

1.8 5.3 0.02 0.07 89 267 Broadleaf plants/ Insect ground 0.3 0.6 0.00 0.01 14 30 Seeds 2.5 7.1 0.03 0.10 126 356 Short grass 1.2/ 3b Ornamental 1.1 3.3 0.01 0.04 53 163 Tall grass 7 day interval ( woody shrubs & vines 1.3 4.0 0.02 0.05 67 201 Broadleaf plants/ Insect ground 0.2 0.4 0.003 0.01 10 22 Seeds 1 Assumes degradation using FATE version 5.0 program with a total foliar residue dissipation half life of 3 days.

2 RQ greater or equal to 0.5 exceeds acute, acute restricted use and acute endangered species RQ greater or equal to 0.2 exceeds acute restricted use and acute endangered species LOCs.

RQ greater or equal to 0.1 exceeds acute endangered species LOCs. 3 RQ greater or equal to 1.00 exceeds chronic LOC.

a Due to reduced egg production, reduced mean egg weight, reduced fertility ra reduced number of hatched ducklings, reduced number of 14 day old survivors and an increased rate of early embryonic deaths. b Maximum number of applications/ year or crop cycle not specified ( assumed 3 applications). 80 Table 5: Mammalian Chronic Risk Quotients for Multiple Applications of Metiram Nongranular ( Broadcast) Based on a labaratory rats ( Rattus norvegicus) NOAEL of 40 ppm a Application Rate Chronic RQ Chronic RQ ( lbs ai/ A)/

Based on Based on Number of Mean EECs Maximum EECs Mean Maximum Applications/ Site/

( Mean EEC/ NOAEL) 2 ( Max. EEC/ NOAEL) 2 EEC ( ppm) 1 EEC ( ppm) 1 Food Items Interval Application Method 34 95 1,342 3,788 Short grass 4.8/ 4 Apples 14 43 568 1,736 Tall grass 7 day interval ground & aerial 18 53 710 2,131 Broadleaf plants/ Insects 3 6 110 237 Seeds 18 51 721 2,037 Short grass 1.6/ 7 Potatoes 8 23 305 933 Tall grass 5 day interval ground & aerial 10 29 382 1,146 Broadleaf plants/ Insects 1 3 59 127 Seeds 40 113 1,605 4,533 Short grass 6.8/ 3b Tobacco 17 52 680 2,077 Tall grass 4 day interval ground 21 64 850 2,550 Broadleaf plants/ Insects 3 7 132 283 Seeds 9 25 357 1,009 Short grass 1.6/ 3b Ornamental 4 12 151 463 Tall grass 7 day interval ( nonflowering plants)

5 14 189 568 Broadleaf plants/ Insects ground 0.7 2 29 63 Seeds 7 19 268 757 Short grass 1.2/ 3b Ornamental 3 9 114 347 Tall grass 7 day interval ( woody shrubs & vines)

4 11 142 426 Broadleaf plants/ Insects ground 0.6 1 22 47 Seeds 1 Assumes degradation using FATE version 5.0 program with a half life of 35 days. EFED uses this value as a default value when the foliar dissipation for a particular pesticide is unknown.

2 RQ greater or equal to 1.0 exceeds chronic risk LOCs.

a Reproductive study, dueto parental toxicity resulting in decreased body weight during gestation and lactation for females and reproductive toxicity resulting in decreased mating performance ( increased precoital time) in the F2 generation ( two generations removed from the original parent generation) b Maximum number of applications/ year or crop cycle not specified ( assumed 3 applications). ii. Mammals As identified in Appendix III, metiram is practically nontoxic ( rat LD 50 > 5,000 mg/ kg) to mammals on an acute basis. Because of this, there is a minimal concern that the acute exposure to metiram presents a risk to mammals, so RQs for acute exposure were not determined. The chronic mammalian risk quotients for multiple broadcast applications of nongranular products are tabulated below in table 5. The results indicate that chronic mammalian LOCs are exceeded for all metiram use patterns listed. 81 82 Table 5a: Mammalian Chronic Risk Quotients for Multiple Applications of Metiram Nongranular ( Broadcast) Based on a labaratory rats ( Rattus norvegicus ) NOAEL of 40 ppm a Application Rate Chronic RQ Chronic RQ ( lbs ai/ A)/

Based on Based on Number of Mean EECs Maximum EECs Mean Maximum Applications/ Site/

( Mean EEC/ NOAEL) 2 ( Max. EEC/ NOAEL) 2 EEC ( ppm) 1 EEC ( ppm) 1 Food Items Interval Application Method 12.7 35.9 508 1,435 Short grass 4.8/ 4 Apples 5.4 16.4 215 658 Tall grass 7 day interval ground & aerial 6.7 20.2 269 807 Broadleaf plants/ Insects 1.0 2.2 42 90 Seeds 5.0 14.0 198 560 Short grass 1.6/ 7 Potatoes 2.1 6.4 84 257 Tall grass 5 day interval ground & aerial 2.6 7.9 105 315 Broadleaf plants/ Insects 0.4 0.9 16 35 Seeds 22.5 63.4 898 2,537 Short grass 6.8/ 3b Tobacco 9.5 29.1 381 1,163 Tall grass 4 day interval ground 11.9 35.7 476 1,427 Broadleaf plants/ Insects 1.8 4.0 74 159 Seeds 4.2 11.9 168 475 Short grass 1.6/ 3b Ornamental 1.8 5.4 71 218 Tall grass 7 day interval ( nonflowering plants)

2.2 6.7 89 267 Broadleaf plants/ Insects ground 0.3 0.7 14 30 Seeds 3.2 8.9 126 356 Short grass 1.2/ 3b Ornamental 1.3 4.1 53 163 Tall grass 7 day interval ( woody shrubs & vines 1.7 5.0 67 201 Broadleaf plants/ Insects ground 0.3 0.6 10 22 Seeds 1 Assumes degradation using FATE version 5.0 program with a half life of 3 days.

2 RQ greater or equal to 1.0 exceeds chronic risk LOCs.

a Reproductive study, dueto parental toxicity resulting in decreased body weight during gestation and lactation for females and reproductive toxicity resulting in decreased mating performance ( increased precoital time) in the F2 generation ( two generations removed from the original parent generation) b Maximum number of applications/ year or crop cycle not specified ( assumed 3 applications) Revised modeling, using a 3 day foliar dissipation half life for metiram, yields the mammalian chronic RQs for metiram in Table 5a. When compared to the chronic RQs provided in Table 5 above, based on a 35 day foliar dissipation half life, substantial chronic risks to birds still exist.

iii. Insects Currently, EFED does not assess risk to non target insects. Results of acceptable studies are used for recommending appropriate label precautions. Since metiram was determined to be practically 83 nontoxic to honey bees ( LD 50 = 437 µ g/ bee) no bee precautionary labeling is required on metiram product labeling.

c. Exposure and Risk to Aquatic Organisms i. Overview Because monitoring data from field locations are not available for metiram, the surface water exposure EECs of metiram are based on results of screening models. Surface water concentrations of metiram were modeled using the Pesticide Root Zone Model version 3.1.2 beta ( Carsel et al., 1997) and Exposure Analysis Modeling System version 2.98.04 ( Burns, 1997) ( PRZM/ EXAMS) for Tier II estimates.

The PRZM/ EXAMS modeling tools used by EFED are designed to be conservative tools; 90% of simulated sites are expected to have environmental concentrations which are lower than the Tier II estimates. EFED uses environmental fate and transport computer models to calculate refined EECs. PRZM simulates pesticide surface water runoff on daily time steps, incorporating runoff, infiltration, erosion, and evaporation. The model calculates foliar dissipation and runoff, pesticide uptake by plants, soil microbial transformation, volatilization, and soil dispersion and retardation. EXAMS simulates pesticide fate and transport in an aquatic environment ( one hectare body of water, two meters deep with no outflow). The EECs have been calculated so that in any given year, there is a 10% probability that the maximum average concentration of that duration in that year will equal or exceed the EEC at the site. The Tier II model uses a single site which represents a high exposure scenario for the use of the pesticide on a particular crop use site. The weather and agricultural practice are simulated at the site over multiple years so that the probability of an EEC occurring at that site can be estimated. The PRZM/ EXAMS modeling approach is an uncertain predictor of water concentrations in estuarine/ marine systems. It is expected, though not empirically demonstrated, that flushing and exchange rates within these systems may differ from those assumed in the existing surface water modeling. In some cases, flushing and exchange may be greater than accounted for in the EXAMS model and actual estuarine/ marine water concentrations may be lower. In other cases tidal entrapment of pollutants may contribute to higher effective pesticide concentrations than have been predicted.

The EECs are used for assessing acute and chronic risks to aquatic organisms. Acute risk assessments are performed using peak EEC values for single and multiple applications. Chronic risk assessments are performed using the 21 day EECs for invertebrates and 60 day EECs for fish.

Input parameters used in Tier II ( PRZM version 3.1.2 beta/ EXAMS version 2.90.04) modeling were selected using Agency guidance ( WQTT/ EFED/ OPP. August, 2000) and EFED calculated degradation rate constants from review of registrant submitted environmental fate studies. A summary, with the environmental fate parameters used in the model for metiram and the output EECs, is provided in Appendix II. For a discussion of these parameters see the Surface Water Monitoring and Modeling section, above, of this assessment 84 Table 6: Metiram Acute Risk Quotients for Freshwater Fish Based On a Rainbow Trout ( Salmo gairdneri ) LC50 of 230 ppb. Application Rate ( lbs ai/ A)/

Number of Acute RQ Applications/ Site/ ( Peak EEC/ LC50) 2 EEC Peak ( ppb) 1 Interval Application Method/

0.43 98.9 4.8/ 4 Apples 7 day interval ground & aerial 0.24 54.5 1.6/ 7 Potatoes 5 day interval ground & aerial 1 Based on PRZM version 3.12/ EXAMS version 2.97.5 modeling. 2 RQ greater or equal to 0.5 exceeds acute high risk, acute restricted use and acute endangered species LOC 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 Metiram acute risk quotients for freshwater fish are tabulated below in Table 6. The results indicate that acute restricted use and acute endangered species LOCs are exceeded for uses on apples and potatoes. Modeling was only performed on these two ( 2) metiram uses since these are the major crop uses for metiram and scenarios for performing PRZM EXAMS modeling for ornamental plantings have not been developed. 85 Table 7: Metiram Acute Risk Quotients for Freshwater Invertebrates Based On a water flea ( Daphnia magna) EC50 of > 358 ppb. Application Rate ( lbs ai/ A)/

Number of Acute RQ Applications/ Site/ ( Peak EEC/ LC50) 2 EEC Peak ( ppb) 1 Interval Application Method/

0.28 98.9 4.8/ 4 Apples 7 day interval ground & aerial 0.15 54.5 1.6/ 7 Potatoes 5 day interval ground & aerial 1 Based on PRZM version 3.12/ EXAMS version 2.97.5 modeling. 2 RQ greater or equal to 0.5 exceeds acute high risk, acute restricted use and acute endangered species LO 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 Metiram's acute risk quotients for freshwater invertebrates are presented in Table 7. The results indicate that the freshwater invertebrate acute restricted use and acute endangered species LOCs are exceeded for uses on apples and potatoes. It should be noted that the metiram EC 50 for daphnia is expected to be greater than 358 ppb since this was the largest concentration tested in MRID No. 44301101 and an EC 50 was not truly established on this supplemental study. Based on this supplemental study it is uncertain whether or not metiram would pose an acute risk to aquatic invertebrates, since the study did not provide a definitive EC 50 . A core study is being required to fulfill this guideline requirement. 86 Table 8: Metiram Acute Risk Quotients for Aquatic Non Vascular Plants Based Upon a Green Algae ( Ankistrodesmus bibraianus ) EC50 of 77 ppb Application Rate ( lbs ai/ A)/ Number of Non Target Plant Applications/ Site/

RQ ( EEC/ EC50) 3 EEC Peak ( ppb) 1 Interval Application Method/

1.28 98.9 4.8/ 4 Apples 7 day interval ground & aerial 0.71 54.5 1.6/ 7 Potatoes 5 day interval ground & aerial 1 Based on PRZM version 3.12/ EXAMS version 2.97.5 modeling.

2 RQ greater or equal to 1.0 exceeds acute risk LOCs. d. Exposure and Risk to Non target Plants: Aquatic Plants Exposure to non target aquatic plants may occur through runoff or spray drift from adjacent treated sites. An aquatic plant risk assessment for acute risk is usually made for aquatic vascular plants from the surrogate duckweed Lemna gibba. Non vascular acute risk assessments are performed using either algae or a diatom, whichever is the most sensitive species. An aquatic plant risk assessment for acute endangered species is usually made for aquatic vascular plants from the surrogate duckweed Lemna gibba. To date, there are no known non vascular plant species on the endangered species list. Runoff and drift exposure is computed from PRZM EXAMS. The risk quotient is determined by dividing the pesticide's initial or peak concentration in water by the plant EC 50 value.

Acute risk quotients for freshwater, non vascular green alga ( Ankistrodesmus bibraianus) plants are presented in Table 8. The results indicate that the non vascular, non target plant acute risk LOCs are exceeded for metiram's use patterns on apples. 87 e. Endangered Species Based on available screening level information there is a potential concern for acute effects on listed birds and freshwater fish species and chronic effects on listed birds and mammals should exposure actually occur. Even though metiram is only slightly toxic to birds, RQs exceed the endangered species LOC ( RQ range from 0.11 to 1.22) at maximum EEC levels. EFED does not expect metiram exposure to pose acute risk to nontarget insects because metiram is practically nontoxic to honeybees ( acute contact LD 50 = 437 µ g/ bee) and there are no incident data reporting adverse effects to honeybees. The Agency does not currently have enough data to perform a screening level assessment for metiram's effects on listed nontarget terrestrial plants, freshwater invertebrates, estuarine/ marine fish, or vascular aquatic plants. There are no nonvascular aquatic plants or estuarine/ marine invertebrate species on the endangered species list.

f. Ecological Incidents The Ecological Incident Information System ( EIIS) ( see Appendix VI for background information) indicated there were no adverse effect incidents to terrestrial or aquatic non target organisms reported in association with metiram's use. 88 APPENDIX V: Relevant Eco toxicity Data Correspondence UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES DP Barcode: D261917 Filename: DCTM_ ARP. wpd MEMORANDUM 2/ 24/ 00 Subject: Request to Upgrade Four Ecotoxicity Studies Using Metiram To: Patricia Moe, Chemical Review Manager Special Review and Reregistration Division ( 7508W)

From: Joanne Edwards, Entomologist Ecological Hazards Branch Environmental Fate and Effects Division ( 7507C)

Through: Tom Bailey, Chief Ecological Hazards Branch Environmental Fate and Effects Division ( 7507C)

EFED has considered BASF's response to EFED's review of four aquatic ecotoxicity studies ( MRIDs 44224401, 44301101, 4430102, and 43199601; see D234011, D237041 and D177394 ). The additional information provided by BASF does not allow for upgrading of these studies. The primary issue with aquatic testing of metiram has been how to deal with its poor solubility ( i. e., variously reported at 2 ppm or less) . EFED and BASF had an understanding that all aquatic ecotoxicity test results would be based on measured and filtered samples.

To date, there are no " core" aquatic studies using ETU as the test substance, and only one " core" study, a rainbow trout acute study, using metiram as the test substance . The rainbow trout LC50 was 0.55 ppm based on measured concentrations. When correcting for dissolved material ( filtered), the LC50 was 0.2 ppm ( MRID 43525001). These results show metiram to be highly toxic to the fish, and indicate the need for label precautionary language, and higher tier testing. These results are in strong contrast to results from previously submitted studies conducted with metiram and ETU, in which the results were based on nominal concentration, and showed ETU and metiram to be practically nontoxic to aquatic animals. These studies have been reclassified invalid ( e. g., bluegill LC50 metiram > 160 ppm ( MRID 40945501); bluegill LC50 metiram between 26 and 42 ppm ( MRID 89 44224401); daphnid EC50 metiram = 2.53 ppm. ( MRID 4097003); rainbow trout ETU LC50> 490 ppm ( Acc. 071589) and daphnid ETU LC50 = 49 ppm ( Acc. 071589).

The registrant is referred to the guidance for how to deal with poorly soluble compounds in EPA's Rejection Rate Analysis ( EPA 738 R 94 0235), in particular to why the Agency considers measured concentrations, rather than nominal concentrations, necessary. The registrant is referred to the individual Data Evaluation Records for the other reasons the studies do not warrant reclassification.

In the case of the green algae study ( MRID 43199601), additional reasons for asking for a repeat study, not listed in the DER, include an inappropriate lighting regime ( 2x recommended) and inappropriate cell inoculum levels ( 4x recommended). The registrant is referred to the guidance in EPA's Pesticide Rejection Rate Analysis ( see pg. 158).

If you have any questions regarding this memorandum, you may contact Joanne Edwards ( 308 6736) or Tom Bailey ( 308 6666). 90 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES DP Barcode: D234011; D237041; D177394 Filename: DCTM_ ARP. wpd MEMORANDUM 4/ 12/ 99 Subject: Ecotoxicity Studies for Metiram To: Anne Overstreet, Chemical Review Manager Special Review and Reregistration Division ( 7508W)

From: Joanne Edwards, Entomologist Ecological Hazards Branch Environmental Fate and Effects Division ( 7507C)

Through: Tom Bailey, Chief Ecological Hazards Branch Environmental Fate and Effects Division ( 7507C)

Attached to this memorandum are Data Evaluation Records ( DERs) for ecotoxicity studies conducted with metiram. A synopsis of each study review is provided below.

MRID 40656901. D. W. Fletcher. 1988. Metiram Technical: 21 Day Acute Oral LD50 Study in Bobwhite Quail; Bio Life Associates LTD; Sponsor: Metiram Task Force; Laboratory Report ID 87 QD 99; no DP barcode This study is classified core, and fulfills the guideline requirement for an acute oral toxicity study with an upland gamebird. The bobwhite LD50 is > 2150 ppm, classifying metiram as practically nontoxic to bobwhite on an acute oral basis.

MRID 44224401. R. Munk. 1996. BAS 222 28 F Acute Toxicity Study on the Bluegill Sunfish ( Lepomis macrochirus RAF.) In a Flow through System ( 96 Hours); BASF Aktiengesellschaft, Ludwigshafen, Germany; Sponsor BASF Corp., Research Triangle Park, NC; Laboratory Report ID 14F0265/ 965056; D234011 91 This study is not scientifically sound, and does not fulfill the guideline requirement for an acute LC50 with a warmwater fish ( Gdln 72 1). The study is classified invalid because the analytical data were questionable and stability/ solubility problems were encountered with the test material. The study must be repeated.

MRID 44301101. Maisch. 1997. Determination of the Acute Effect of BAS 222 28 F ( Metiram) on the Swimming Ability of the Water Flea, Daphnia magna; BASF Aktiengesellschaft, Ludwigschafen/ Rhine, FRG; Sponsor: BASF Corp., Research Triangle Park, NC; Laboratory Report ID 97/ 10538; D237041 This study is scientifically sound, but does not fulfill the guideline requirement for an acute LC50 with a freshwater invertebrate ( Gdln 72 2). The study is classified supplemental because ( 1) an EC50 was not established; ( 2) there was a high variability in analytical results; and ( 3) analytical measurements were not made on new solutions in this static renewal test. Based on the median analytical recover rate of all tested concentrations ( 51.1%), the reported 48 hour EC50 was > 358 ppb, which classifies metiram as highly toxic to Daphnia magna. The study must be repeated.

MRID 443011 02. Maisch. 1997. Determination of the Chronic Effects of BAS 222 28 F on the Reproduction of the Water Flea Daphnia magna STRAUS in a Flow Through Test System; BASF Aktiengesellschaft, Ludwigshafen/ Rhine, Germany; Sponsor: BASF Corp., Research Triangle Park, NC; Laboratory Report ID 97/ 10521; D237041 This study is not scientifically sound, and does not fulfill the requirements for a freshwater invertebrate life cycle test ( Gdln 72 4). The study is classified invalid because: ( 1) the measured concentrations were highly variable ( measured 6 to 106% of the nominals); ( 2) the control concentrations appeared to be contaminated; ( 3) ephippia were produced in the control group; and; ( 4) dry weight was not measured. The study must be repeated.

MRID 43199601. G. P. Dohmen. 1990. Effects of BAS 222 28 F on the Growth of the Green Alga Ankistrodesmus bibraianus; BASF Aktiengesellschaft, Limburgerhof, Germany; Sponsor: BASF Corp., Research Triangle Park, NC; Laboratory Project ID: P 9 0  E008 This study is scientifically sound but does not fulfill the guideline requirements for an algal toxicity test because the test was only conducted for 72 hours and the test species was not the required green alga species. The study is classified supplemental. The 72 hour EC 50 and NOEC for A. bibraianus exposed to metiram were 0.077 and 0.013 ppm, respectively.