### 2 

# Table of Contents

1 Executive Summary

................................ ................................ ................................ .............. 3
2 Introduction

................................ ................................ ................................ ........................... 7
3 Use Characte rization

................................ ................................ ................................ ............ 8
3.1 Labelled Use

................................ ................................ ................................ ........................ 8
3.2 Usage

................................ ................................ ................................ ................................ .... 8
4 Conclusions from P revious Risk Assessments

................................ ................................ .... 9
4.1 Ecological Risk Assessment

................................ ................................ .............................. 10
4.2 Drinking Water Exposure Assessments

................................ ................................ ............. 10
4.3 Clean Water Act Programs

................................ ................................ ................................ 11
5 Environmental Fate and Transport

................................ ................................ .................. 12
5.1 Metiram

................................ ................................ ................................ .............................. 12
5.2 The Major Me tiram Degradate: Ethylenethiourea (ETU)

................................ ................. 24
5.3 Determination of the Stressor of Concern for Ecological Risk Assessment

..................... 29
6 Receptors

................................ ................................ ................................ ............................. 33
6.1 Effects to Aquatic Organisms

................................ ................................ ............................ 33
6.2 Effects to Terrestrial Organisms

................................ ................................ ........................ 37
6.3 Ecological Incidents

................................ ................................ ................................ ........... 41

7 Exposure Pathways of Concern

................................ ................................ ......................... 41
8 Analysis Plan

................................ ................................ ................................ ....................... 43
8.1 Stressor s of Concern

................................ ................................ ................................ .......... 43
8.2 Measures of Exposure

................................ ................................ ................................ ........ 43
8.3 Measures of Effect

................................ ................................ ................................ ............. 43
9 Endangered Species Assessments

................................ ................................ ...................... 43
10 Endocrine Disruptor Screening Program

................................ ................................ ......... 44
11 Preliminary Identification of Data Gaps

................................ ................................ .......... 44
11.1 Environmental Fate

................................ ................................ ................................ ..... 44
11.2 Effects

................................ ................................ ................................ ......................... 46
12 References

................................ ................................ ................................ ............................ 57

### 3 

# 1 Executive S ummary

The Environmental Fate and Effects Division (EFED) has completed the problem formulation for the ecological risk, environmental fate, endangered species, and drinking water assessments to be conducted as part of the registration review of metiram . The pro blem formulation describes the
methods planned to be used during the completion of drinking water and ecological risk assessments in support of registration review and provides an ove rview of the environmental fate, ecological effects , and potential risks associated with the use of metiram as well as uncertainties unique to risk assessment of metiram . This document also identifies additional studies that would be beneficial to the conduct of an ecological risk assessment to parent metiram and the primary degradation product, ethylene

- thio

- urea (hereafter referred to as ETU)

. Major environmental fate and ecological effects data needs as well as uncertainties related to the assessment are stated
hereunder :

Uncertainties and Data Gaps

Environmental Fate

Some of the submitted studies for this chemical were either un acceptable or supplemental. The problems identified in these studies were mainly related to characterization/quantification of

m etiram residues . For example, identification/quantification of chemicals in the m etiram residues were largely dependent on the TLC method which was affected by poor separation and the occurrence of degradation caused by the solvent systems employed. In order to conduct t he future risk assessment with minimum uncertainties, the registrant is requested to submit the following
studies:

Hydrolysis (OCSPP 835.2120): A new guideline hydrolysis study for a m etiram active ingredient to which solubility is known (pre

- determined b y a guideline study) with concentration below this

pre

- determined solubility

. In this study, the starting residues, just after dissolution should be characterized and tracked to the end of the study;

Aerobic soil metabolism (OCSPP 835.4100): A new guideli ne study for the same metiram active ingredient used in the hydrolysis study in two different soils from known areas where the pesticide is used with varied pH, organic matter content and cation exchange capacity ;

Anaerobic Aquatic metabolism (OCSPP 835.4 00): A new guideline study for m etiram in two water/sediment systems;

Aerobic soil metabolism (OCSPP 835.4100): A new guideline study for ETU i n the same two soils used in the requested aerobic study;

Aerobic Aquatic metabolism (OCSPP 835.4300): A new guideline study for ETU in two water/sediment systems ; and

Anaerobic Aquatic metabolism (OCSPP 835.4400): A new guideline study for ETU in two water/sediment systems.

### 4 In these studies, the registrant is requested to better characterize and if poss ible identify the un

extracted residues. This is because these residues were found to be more toxic than parent in submitted sediment toxicity studies. Additionally, complete identification, quantification of all degradates are expected along with tracking their formation and decline. Furthermore, the following should be observed:

(1) The maximum single application rate for metiram is 2.7 lbs a.i/A, therefore, the application rate to the aerobic soil and aquatic studies may be conducted with concentration at or below the solubility of 2 ppm for metiram. At this solubility, metiram as a parent is not expected to be present. Therefore, parent residue is what is applied to the soil /sediment and it should be analyzed before application and throughout the study dur ation. Due to the fact that there are transient species forming early it is recommended that shorter intervals are chosen for the fi rst week of the study;

(2) The objective of meta bolism studies are to track the formation/decline of all transient species/degradates in metiram residue applied to the soil /sediment ; and

(3) For all metabolism studies requested for mancozeb residues and ETU, the registrant should show efforts to extract and identify residues that may be left associated with soil or sedime nt following EFED un

- extracted residues guidance 1



### .

ECM/ILV (OCSPP 835.6100) : The registrant is requested to submit environmental chemistry method and associated independent laboratory validation ( ECM/ILV ) studi es for determination of
metiram and ETU in s oil and metiram only in water.

Ecological Effects

The following uncertainties are identified for metiram:

Extent of toxicity to larval and juvenile h oney bees

Currently, there are data available that characterize the acute contact and acute oral toxicity of
metiram to adult honey bees. The extent to which metiram exerts toxic effects on honey bee larvae or juvenile honey bees is unknown. Further toxicity data that is recommended below is needed to characterize this uncertainty.

Extent of Toxicity of un

- extracted residues to other sediment

- dwelling invertebrates

As this assessment will show, the un

- extracted residues of metiram form immediately after
introduct ion in an aerobic aquatic system and steadily increase to approximately 25% of the applied radioactivity after 14 days and remain relatively stable after 100 days. Sediment dwelling invertebrates are expected to be exposed to these residues as part or all of their life cycle is spent

1 URL: http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/environmental_fate_tech_team/Unextrac ted_Residues_in_Lab_Studies.htm

### 5 in contact with the sediment and pore water. Currently, there are two subchronic (10

- day) sediment toxicity studies conducted with parent metiram ( spiked sediment system) that are in review with one study conducted with the f reshwater midge ( Chironomus dilutus ) and one study conducted with the estuarine/marine amphipod ( Leptocheirus plumulosus ). Available data for
another EBDC chemical (mancozeb) shows enhanced toxicity by approximately an order of magnitude of the un

- extract ed residues as compared to parent mancozeb in 10

- day spiked sediment studies with the freshwater midge. As metiram and mancozeb share structural similarities as well as the propensity to undergo decomposition and form un

- extractable residues, it is uncert ain to the
extent these un

- extracted residues will show increased toxicity to sediment dwelling invertebrates as compared to parent metiram. It is also an uncertainty the extent of toxicity that chronic exposures beyond 10 days of these un

- extracted resid ues would have to sub lethal measures of effects including reproductive endpoints.

Extent of toxicity and bioavailability of un

- extracted residues to terrestrial organisms

As this assessment will show, the un

- extracted residues of metiram form immediately after introduction into an aerobic soil system (up to 66% of the applied radioactivity) at Day 0 and remain relatively stable for approximately 30 days before undergoing gradual mineralization to
CO 2 

### . It is an uncertainty if similar formation rates are observed when metiram is sprayed on foliage. Additionally, it is an uncertainty the extent of the toxicity and bioavailability of these residues to terrestrial taxa like birds, mammals, and terrestrial invertebrates. Although available
ecotoxic ity studies show that the major metiram degradate, ETU, is less toxic to terrestrial organisms as compared to parent metiram, maximum ETU residues in the soil reach approximately 11% after 2 days before steadily declining with time.

Hereunder is a list of requested studies:

Avian Acute Oral Toxicity (OCSPP 850.2100)

. There is currently one acute oral toxicity study
for birds conducted with metiram. Two studies with differing species are recommended to serve as surrogates for all avian species for the ac tual oral route of exposure. Available records indicate the submission of an acute oral toxicity study with a passerine species for another Ethylene

- bis

dithiocarbamate (EBDC) chemical, mancozeb ( canary, Serinus canaria , MRID 48515401). A preliminary rev iew of this study indicate s regurgitation was observed in 4 of the 5 treatment groups. The observation of regurgitation occurred in a dose

- dependent manner with no observation at the lowest treatment group (259 mg a.i/kg

- bw) and 60, 80, 100, and 100% of t he birds at the 432, 720, 1200, and 2000 mg a.i/kg

- bw, respectively. This study indicates that passerines may be more sensitive to EBDC chemicals including metiram than waterfowl or upland game bird species. An avian acute oral toxicity with a passerine species is recommended to address this uncertainty.

Avian Reproduction Test (OCSPP 850.2300). Currently, there are two chronic avian reproduction studies available for metiram. In the study with the bobwhite quail

, several deficiencies including high control mortality and a larger than acceptable incidence of cracked

eggs were observed in the control group. These deficiencies limit its use in quantitative risk

assessment. The companion mallard duck study was class ified as acceptable. At currently labeled metiram rates and the acceptable chronic NOAEC from the mallard study, chronic avian RQs

### 6 would reach 55, which is above the chronic LOC of 1. Despite the fact that parent metiram is shown to rapidly degrade to le ss than 15% parent within a day, these transformation rat e s are derived from soil metabolism studies. There is an uncertainty regarding the behavior of parent metiram when sprayed on foliage as currently labeled practices permit via ground or aerial spra y. There is not enough information currently present to assume the degradation rates observed via aerobic soil metabolism pathway would be similar on foliage. Additionally, the bobwhite quail may potentially prove to be the more sensitive species as it w as in the available sub

- acute dietary studies for metiram. Therefore, an additional avian reproduction study with the northern bobwhite quail is recommended to address this uncertainty.

Non

- Guideline study (OECD TG 237) (Tier 1): Honey Bee Larvae Acute Oral Toxicity (Tier I) 2 

### Honey bees can be exposed to pesticides through multiple pathways including contact with sprays and dusts and through ingestion of residues in food/water ( e.g ., pollen/nectar and water used to maintain colony temperature). Worker bees foraging on flowers for pollen and nectar can be repeatedly exposed to residues in pollen and nectar either through direct contamination of these matrices by foliar sprays of the active ingredient. Residues can in turn be brought back to bee
colonies where in

- hive bees including young adult and developing brood ( i.e ., eggs, larvae and pupae) may be exposed. EPA guidance on assessing the risk of pesticides to bees identifies a suite of laboratory

- based studies intended to facilitate screening for pote ntial acute and chronic effects
to individual adult and larval bees.

A study examining the acute contact and acute oral toxicity to the adult honey bee s is currently in review (MRID 49403401 ). There are no data available, however, to characterize the p otential

acute toxicity to larval honey bees. Honey bee larvae have often been shown to be more sensitive to chemicals than adults and therefore this study is r ecommended to address this uncertainty. No protocol needs to be submitted to the Agency before the initiation of this study as guidance for its parameters are documented in OECD Test Guideline 237. Pending the results of this study, higher tiered ( e.g. semi

- field) studies as well as residue studies may be required.

Non

- guideline study (Tier 1): Honey Bee Larvae Chronic Oral Toxicity. As mentioned above, EPA guidance on assessing the risk of pesticides to bees identifies a suite of laboratory

- based studies intended to facilitate screening for potential acute and chronic effects to i ndividual adul t and larval bees. T here are currently no data available to characterize the acute or chronic toxicity to honey bee larvae. EFED recommends that a protocol (following the OECD draft test guideline document, February 25, 201 4 ) 3 

### be submitted for review and approval by the Agency prior to initiation of this study. Pending the results of this study, higher tiered ( e.g. semi

- field) studies as well as residue studies may be recommended

.

Non

- guideline study: Honey Bee Adult Chronic Oral Toxicity (Tier 1). E PA guidance on assessing the risk of pesticides to bees identifies a suite of laboratory

- based studies intended to facilitate screening for potential acute and chronic effects to individual adult and larval bees. The
10

- day toxicity study with young adult bees provides no

- observed adverse effect level (NOAEL)

2 Depending on the design of the “Honey Bee

– 21

- day repeated dose chronic larval toxicity,” study, a 72

- hour LD 50 value may be derived from this study. If that is possible, it would obviate the need for this study.

3 http://www.oecd.org/che micalsafety/testing/Draft_GD_honeybee_larval_tox_repeated_exposure_25_February_201 4.pdf

### 7 and lowest

- observed adverse effect level (LOAEL) for assessing chronic effects. Risk estimates based on these data will be considered along with other lines of evidence to determine whether higher

- tie r studies are needed at the whole colony level. EFED recommends that the registrant submit a protocol and consult with the Agency prior to study initiation.

Non

- guideline study : Field Trial of Residues in Pollen and Nectar (Tier 2): Submission of studies for crops of concern that evaluate residue s in plant parts ( e.g. pollen and nectar) may be of high value depending on the results of the screening level risk assessment and the Tier I larval bee toxicity study. If refinements to t he screening level risk assessment for honey bees are needed, these studies will allow for a more refined exposure analysis when applications are made at bloom. This chemical is of low toxicity to adults, but applications at bloom could contaminate pollen and nectar that adult foragers bring back to the colonies, resulting in potential exposures to the brood. In order to evaluate this exposure pathway, these residue studies would assess metiram residues in pollen and nectar. EFED recommends that the regi strant submit a protocol and consult with the Agency prior to study initiation.

Non

- guideline study : Semi

- Field Testing for Pollinators (Tunnel or Colony Feeding Studies) (Tier 2). Screening level and refined Tier 1 risk assessments with the honey bee l arvae may indicate the need to progress to higher tier toxicity testing under semi

- field conditions. In evaluating the effects of metiram on honey bees at the colony level, there are uncertainties relating to the growth and reproduction of the colonies an d measurement endpoints that relate to brood development and production. Semi

- field testing data can be used to address these uncertainties with either a tunnel or colony feeding study experiment design. EFED recommends that the registrant submit a proto col and consult with the Agency prior to study initiation.

850.3040: Field Testing for Pollinators (Tier 2 or 3): Screening level and refined Tier 1 risk assessments with the honey bee larvae may indicate the need to progress to higher tier toxicity
testi ng under field conditions. In evaluating the effects of metiram on honey bees at the colony level, there are uncertainties relating to the growth and reproduction of the colonies and measurement endpoints that relate to brood development and production. Field testing data can be used to address these uncertainties. EFED recommends that the registrant submit a protocol and consult with the Agency prior to study initiation.



# 2 Introduction

Metiram [CAS name: metiram; IUPAC name: zinc ammoniate ethylenebis (dithiocarbamate)

– poly (ethylene thiuram disulfide); CAS number 9006

- 42

- 2; PC Code 014601; and molecular
formula C 12 

### H 12 

### N 6 

### S 16 

### Zn ], is an ethylene bis dithiocarbamate (EBDC) non

- systemic fungicide with protective action on contact. The dithiocarbamate gro up also includes the fungicides mancozeb, thiram, zineb, and ziram. Its specific mode of action (MOA) is unknown and is classified by the code M3 (multi

- site action) by the Fungicide Resistance Action Committee (FRAC 4 

### ).

4 Fungicide Resistance Action Committee: URL: http://www.frac.info/docs/default

- source/publications/frac

- code

list/frac

- code

- list

- 2015

- finalC2AD7AA36764.pdf (accessed June, 2015)

### 8 

# 3 Use Characterization

**3.1 Labelled Use** 

Metiram is registered for use on potato es to control early and late blight. It is also registered for use on apples to control scab and rust diseases. Metiram is effective in controlling these diseases and also plays an important role in resistance manag ement program s because it has multisite mode of action against fungal pests.

Based on the Label Use Information System ( LUIS ) report dated 08/14/2014, there are two labels for use on apples and potatoes (EPA registration numbers: 7969

- 105 and 7969

- 321 ) an d one Special Local Need (SLN Registrations under FIFRA Section 24 (c) (EPA registration number:
FL980001 ). Metiram i s for m u lated only as water dispersible granules ( dry flowable “DF”)
and applied as liquid spray using gro u nd, a i r c

r a

ft, or through irrigation systems (chemiga t i on). Table 1 contains a summary of all labeled uses

.

Table 1 Metiram use patterns

Crop Use Pattern Application Parameters 1

Notes MSR MNA MTR MAI

Apple 2.4 7 16 .8 7 A e rial or Ground Foliar sprays ; The extended application schedule ; PHI=77 days Can be applied ; Pre

- bloom 3.6 x 3= 10.8 lbs.ai/A The schedule for the two application s may be combined or integrated

Potatoes 1.6 6 9.6 5 A e rial or Ground Foliar sprays and Chemigation Ornamental in FL only (SLN) 2 1.6 10 16.0 7 G round Foliar spray and Chemigation

1 Application Parameters: MSR= maximum single rate (lbs a.i./acre), MNA = maximum number of applications,

MTR = maximum total rate (lbs. a.i./acre/year), and MAI = Minimum intervals in days. Important Note : Rates specified in the label s for apples and potatoes as “ per crop cycle ” are assumed to be per year and labels are to be modified, by registrants, accordingly.

2 It is noted that MTR of 16 lbs. a.i/A/Year for ornamentals are calculated from label specified MSR and MNA as
follows 1.6 x 10= 16 lbs. a.i/A/Year



### It is important to note that labelled uses summarized above are based on available information as of the date of the LUIS report and application parameters are chosen from labels containing the highest rates and minimum application intervals. Registrants are requested to review information presented in Table 1 , above and correct/add missing information.



## 3.2 **Usage**

From the metiram BEAD chemical profile (BCP) drafted by the Biological and Economic Analysis Division (02/05/2015) metiram use in terms of pounds a.i. applied in the U.S. averaged 765,000
lbs

. per year on approximately 400,000 acres treated. The average rate a.i over this time (1998

– 2012) period was 1.91 lbs

. a.i/A. During this same time period, for pounds applied and acres treated, there has been a sharp decline in usage primarily driven by the reduction of usage on apple s. During the 2008

- 2012 time frame, the crop with most pounds applied has been potatoes, representing approximately 60% of the total pounds applied. The average rate on potatoes is 1.37

### 9 lbs

. a.i/A, while apples (the only other registered agricultural crop) had an average rate of 2.65 lbs

.
a .i/A. Percent crop treated (PCT) values, that represent the percent of total crop acreage that a given pesticide is applied on are 10% for potatoes and 5% for apples.

Metiram does not have curative properties and therefore it is used in combination and /or in alternation with systemic fungicides (such as azoxystrobin, propiconazole) for season long disease control and resistance management. Metiram is an important fungicide for use on apples and potatoes because no fungal pest has developed resistance a gainst this fungicide since its registration in 1948. The decline in usage may be due to registrations of new generations of fungicides (such as azoxystrobin, pyroclostrobin, zoxamide) for the control of these fungal diseases
while metiram remained as a t ool for resistance management.



# 4 Conclusions from Previous Risk Assessments

Two main risk assessments were conducted for m etiram and its main degradate ETU:



## (1) Environmental Fate and Ecological Risk As sessment for Metiram, Section 3 Reregistration
for Control of Fungal Diseases on Potatoes, Potato seed, Certain Ornamental Plants and Tobacco Seedling Plants (Phase 3 Response) dated June, 2005 which was accompanied by the Environmental Fate and Ecological Risk Assessment for Ethylenethiourea (ETU) a Common Degra date of the Ethylene bis di

- thio carbamate fungicides (EBDCs): M ancozeb

, M etiram

, and M aneb (Phase 3 Response),” dated June , 2005. The two documents were prepared by
EFED for the Reregistration Eligibility Decision for Metiram ( RED) ( Document EPA 73

- R

05

- 017 dated August , 2005) ;



## (2) Risks of Metiram and Maneb Uses to the Federally Listed California Red Legged Frog ( Rana aurora draytonii ) dated October, 2007

.

This problem formulation updates conclusions from r ecent risk assessments

, includ ing the following:

• Changes in labelled use patterns following the RED required mitigation measures which included: use patterns that are ineligible for reregistration and changes in application rates, procedure and intervals for some crops;

• Modify the previ ous assignments for the stressor of concern following new submittals
i ncluding:

o Fate studies with better characterization/quantification of m etiram residues;

o New ecological toxicity studies for ETU

, the major degradate of m etiram ; and

o New sediment toxicity studies.

### 10 

## 4.1 **Ecological Risk Assessment**

As stated previously, t he Agency has completed two main ecological risk assessments on m etiram
that serve as a basis for this problem formulation

. It is very important to note that the previous ecological risk assessments conservatively considered the stressor of concern to be the “ Metiram complex ’ which was defined to include all of its residues : ethylene thio

- urea (ETU), ethylene urea (EU), Ethylene

- bis

- isothiocyanate sulfide (EBIS) and Hydantoin (HYD) an d the un

- extracted
residues (UER)

. An analysis was conducted to re

- examine this finding based on the availability of data since the time of these previous assessment. Details of this can be found in Section 5.3. Previous risk findings are summarized in Ta ble 2

.

Table 2

. Summary of risk concerns i dentified for m etiram in previous a ssessments *

Birds Mammals Terr.
Plants Terr.
Inverts Fish BCF Aquatic
Inverts Aquatic
Plants Groundwater
Contamination Persistence Degrad at es of Concer n

Yes Yes NA NA Yes NA 1 No Yes Yes 2 Yes 3 The Metiram
C omplex

* “ Yes ” = at least one LOC has been exceeded in previous assessments; “ No ” = LOCs have not been exceeded in previous assessments; “ NA ” = RQs have not been calculated previously

1 Due to the very low K OW of 6

- 83 ; noting that no fish bio

- accumulation study was submitted

2 Based on ETU, the degradate of concern of m etiram which is characterized by high solubility and low K OC (288 L/kg)

3 Based on only mineralization of the “ Metiram complex” to CO 2

.



## 4.2 **Drinking Water Exposure Assessments** 

Ethylenethiourea (ETU) is the common degradate of all Ethylene

- bis

- dithiocarbamates (EBDCs) fungicides including m etiram

. ETU, a group B2 carcinogen, was established to be the drinking water stressor resulting from the use of all EB DCs. Several EFED drinking water memos were generated covering original/additional new uses of all or any of the EBDCs for the estimated drinking water concentrations (EDWCs) of ETU for use in human risk assessments (DP Barcode: 290057 dated May 7, 2003; DP Barcode: D290057 dated August 26, 2004; DP Barcodes: 323141/3
d ated August 11, 2006; DP Barcode: 397306 dated July 3, 2012; and DP Barcode: 420706 d ated September 8, 2014).

For surface water, EDWCs were calculated using the linked PRZM and EXAMS simula tion models alone on the assumption of very rapid degradation of the parent EBDC pesticide to ETU on a mole per mole basis. Following the submission of two

- year targeted ETU monitoring data by the EBDC Task force, the chronic long term average EDWC was based on monitoring while
the acute EDWC remained to be based on PRZM/EXAMS modeling. For ground water, a single acute/chroni c EDWC was derived from community water system intake concentration of a targeted groundwater monitoring study conducted by the EBD C Task F orce from 1999 to 2003. Targeted monitoring data were submitted under MRIDs: 45570301; 45708301; 45836401 and
4614540 1. Table 3 contains a summary of the current Tier II EDWCs of ETU which was used for human health drinking water risk assessment

.

### 11 Table 3 Tier II EDWCs (in ppb of ETU ) for human health drinking water risk assessment

Stressor Acute EDWC Surface Water ( PRZM/EXAMS Modeling ) Chronic Surface Water EDWC (Monitoring detection limit) for Non

cancer / Cancer chronic Acute and Chronic Ground

Water EDWC (Monitoring)



### ETU 25.2* 0.1 0.21

* This is the highest value in a range of EDWC values which are expected to be between 0.1 ppb (the detection limit) and 25.2 ppb (the highest peak value after adjustment by the then 0.87 national PCA).



### Requested d ata

, from this registration review for m etiram and ETU will be considered for the
determination of EDWCs for E TU resulting from m etiram degradation. An updated drinking water assessment may be needed as part of the future Registration Review process. If a new drinking water assessment is need ed, EFED will include recently revised percentage crop area (PCA) factors, revised drift factors as well as the use of current SWCC and PRZM

- GW models to determine EDWCs in surface and ground waters, respectively. Use of monitoring data for the acute
and c hronic ground water EDWCs will be dependent on modeled PRZM

- GW EDWCs.



## 4.3 **Clean Water Act Programs**

Metiram and its major degradate ETU were not identified as a cause of impairment for any water bodies listed as impaired under sectio n 303(d) of the Clean Wa ter Act and no Total Maximum Daily Load (TMDL) criteria have been developed for the two chemicals (Refer to URL: http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=88
5 , accessed 03 / 08/2015 )

.

A summary of fish/invertebrates acute/chronic a quatic benchmarks have been established only for

ETU (Table 4 ). However, no acute non

- vasc ular/vascular plants or Office of Water aquatic life criteria (maximum & continuous concentrations) were established for either Metiram or ETU (Refer to URL: http://www.epa .gov/oppefed1/ecorisk_ders/aquatic_life_benchmark.htm

, accessed 03/08/2015).

Table 4 OPP Aquatic l ife b enchmarks for fresh water (μg/ L) for ETU

Fish Invertebrates

Acute 1 Chronic 2 Acute 3 Chronic 4

> 251
, 000 37
, 320 134
, 500 2

1 Benchmark = Toxicity value x LOC. For acute fish, toxicity value is generally the lowest 96

- hour LC50 in a standardized test (usually with rainbow trout, fathead minnow, or bluegill), and the LOC is 0.5.

2 Benchmark = Toxicity value x LOC. For chronic fis h, toxicity value is usually the lowest NOEAC from a life

cycle or early life stage test (usually with rainbow trout or fathead minnow), and the LOC is 1.

3 Benchmark = Toxicity value x LOC. For acute invertebrate, toxicity value is usually the lowest 48

- or 96

- hour
EC 50 or LC 50 in a standardized test (usually with midge, scud, or daphnids), and the LOC is 0.5.

4 Benchmark = Toxicity value x LOC. For chronic invertebrates, toxicity value is usually the lowest NOAEC from a
life

- cycle test with invertebrates (usually with midge, scud, or daphnids), and the LOC is 1.

### 12 Any data submitted or otherwise located as part of the registration review process may be used to update aquatic life benchmarks, if applicable.



# 5 Environmental Fate and Transport

**5.1 Metiram** 

A mixture of 5.2 parts by weight (83.9%) of ammoniates of {ethylenebis(dithiocarbamato)} zinc with 1 part by weight (16.1%) ethylenebis {dithiocarbamic acid} bimole cular and tri molecular cyclic anhydrosulfides and disulfides

. The structure contains four monomer units and b ased on the molecular weight, it contain s : 77.3 % EBDC , 17 % Zn +2 

### and 4.7 % NH 3



### . Hereunder is the chemical structure, f ormula, name and molecular weight

.

Formula: C 16 

### H 33 

### N 11 

### S 16 

### Zn 3 

### ; Molecular Weight = 1088.6 g mole

- 1 

### ; IUPAC Name: zinc ammoniate ethylene bis(dithiocarbamate)

- poly[ethylenebis(thiuram disulfide)] ; CAS Name: tris [ammine

- [ethylen e bis(dithiocarbamate)]zinc(II)][tetrahydro

- l ,2,4,7

- dithiadiazocine

- 3,8

- dithione] p olymer ; and CAS Number: 9006

- 42

- 02 ; EPA PC code: 014 601

The m etiram polymer has a unique water solubility property as it decomposes in water within
hours under acid ic , neutral

, and alkaline conditions. Complete decomposition of the polymer structure into monomeric units appears to be dependent on the concentration of the polymer. This concentration was reported, by the re gistrant, to equal 2 ppm

. It appears that solubility is dependent on the source of the m etir am and that t he process of decomposition by water is probably related to breakage of the polymeric chains into monomeric units as shown in Figure 1

. In this respect, the process of decomposition is probably associated with abiotic hydrolysis and therefore the whole process may be referred to as decomposition/hydrolysis. Additionally, it is important to note that parent studies should be conducted using metiram with predetermined solubility. C

C S

S S S

Zn (NH 3 ) 

### N

N

H H



## Metiram C

C S

S S N

N H

H S 3 X

X>1

### 13 Metiram Monomer ( EBDC anion ) 

# + Zn +2



### Figure 1 Expected decomposition/hydrolysis process for m etiram in water

The length of the polymer chains

, of the m etiram active ingredient

, may be related to the particle size of the active ingredient which may be related to the manufacturing/formulation processes

. Finer particle size is expected to contain shorter polymer chains causing more s usceptibility to the process of decomposition into shorter or monomeric chains by solution /hydrolysis in water.

In the field, m etiram is expected to be applied into moist plant foliage and reach, upon application
and later due to wash

- off, a moist soil sy stem. In addition lesser quantities are expected to reach aquatic systems by drift (usually estimated to be 4

- 16% depending on type of application and nature of the assessment). Therefore, the process of decomposition /hydrolysis of m etiram into its

monome ric units is expected to occur in soil and water/sediment. The maximum single application
rate of m etiram range s from 1.6 to 3.6 lbs. a.i/acre. Upon application, the maximum expected
concentrations of m etiram in the soil system will probably be in the range of <0.8 to <1.8 ppm depending on how much of the applied reach es the soil

. The concentration in aquatic systems is expected to be lower

. In contrast, reported solubility of 2 ppm suggests that the decomposition /hydrolysis process will be impo rtant at these concentration s and that its importance will probably depend on the nature of the polymer and the availability of moisture. In dry conditions the importance of this process is expected to be relatively low er than moist conditions

.

Based on the fact that m etiram

, as a polymer

, is expected to be short lived in the environment

. It is necessary to obtain exposure data for m etiram as well as the residues forming in soil and water/sediment systems following the decomposition/hydrolysis/process

.

(a) Physical Chemical Properties and A biotic Transformation

P hysical and chemical properties and abiotic transformation of m etiram are included in Table 5

.

Table 5 Physical/chemical properties and abiotic transformation of m etiram 

## N C

N H

H S -



## N C S - 

## N

Property Value Reference 1

n

- octanol

- Water Coefficient (K OW ) 6 to 83 ; based on its reported log of 0.78 to 1.92 Product Chemistry Vapor Pressure 7.5 x 10

- 8 torr @ 25 o C Henry's Law constant 5.4 x10

- 8 atm. m 3 mole

- 1 @ 25 o C (Based on solubility of 2 ppm) Calculated

Hydrolysis half

- life (t 1⁄2) 1.4 to 3.1 days @ pHs 5, 7 and 9 and 20

- 25 o C ; Uncertain values 2 001467

- 64 (S) 

## Metiram Polymer

### 14 Hydrolysis data suggest that abiotic hydrolysis appears to be fast and cause s degradation of the
monomeric units of m etiram that is expected to form initially upon dissolving the polymer in water

. ( Table 5 ). Therefore, the fate of m etiram polymer chains appear to be affected significantly by
two processes. The first process i s the breakdown of polymeric parent into monomeric units of
EBDCs with the loss of the metal ions ( Figure 1 , above) upon dissolution in water

. The second
is abiotic hydrolysis of the monomeric units

. The combined decomposition/ hydrolysis

, results in
the formation of transformation products observed in the hydrolysis study (EBIS, Carbimid, E T U

, EU and HYD )

. Although the study gives certainty that m etiram parent is h ighly affect ed by hydrolysis, there are many uncertainties in this study that prevent accurate conclusions on the hydrolysis p rofile for polymeric m etiram and resultant residues

. Uncertainties are identified in the
footnotes in Table 5

. Therefore, the registrant is requested to submit a new hydrolysis study for a

m etiram active ingredient to which solubility is known ( pre

- determined by a guideline stud y ) starting with concentration below this pre

- determined solubility

.

Furthermore , d ata in Table 5 indicate that m etiram is not expected to partition into the air from
dr y/wet soils or from water ( low vapor pressure and Henry’s Law constant). However, it could
move with drift. The n

- octanol

- water partitioning coefficient suggests low bio

- con centration potential for m etiram in aquatic organisms like fish and data suggest that photolysis in water/on soil are not important in dissipation of metiram in the environment

.

(b) Biotic Transformation

As stated previously, fate data will be presented for metiram and major constituents of metiram residues. A summary of this data is presented in Table 6

. Major Transformation Products: Carbimid, ETU, EU, EBIS, HYD and
others 3 001551

- 89 (S) &
001619

- 37 (S )

Aqueous photolysis t 1⁄2 Stable (Based on d ata from water suspended metiram suggesting that degradation is generally controlled by hydrolysis rather than photolysis ) 001551

- 90
with addendum
001619

- 38 (A )

Soil photolysis t 1⁄2 Stable (Based on d ata suggesting that degradation was only slightly more significant in irradiated samples compared to those maintained in the dark ) 001570

- 31 (A )

1 A= Acceptable; S= Supplemental ;

2 Half

- lives are uncertain because the test substance (metiram) parent was applied at 16.7 ppm which is higher than it s solubility of 2 ppm. Additionally, suspensions were prepared by sonication that is expected to reduce p article size which may
shorten determined half

- lives. Additionally, metiram parent was determined by the CS 2 method which is expected to result in longer half

- lives because most of the degradation products contain sulfur that produces CS 2 resulting in higher metiram concentrations and longer half

- lives.

3 T hese are the transformation products identified in the solubilized phase of 1,600

- 2,160 ppm water buffered suspension at pHs of 3, 5, 7 and 9. Degradation products were identified by radio

- scintillation counting and TLC on silica gel plates/HPLC with spectral photometer. Although identification of the degradates may be acceptable

, quantification is uncertain due to expected continuous production of these degradates from un

- degraded parent that is expected to be present due to the extremely high concentration of parent used in the study.

### 15 Table 6 Summary of environmental fate properties of the metiram and residues

Property Value for Metiram Parent & Residues MRID Reference 1

Aerobic soil t 1⁄2 Metiram parent 0.3 days (Observed DT 50 ) in Soil 1 : Cashmere loamy sand soil (77% sand, 16% silt, 7% clay, pH 6.6, 0.8% organic carbon, and CEC of 12 meq/100g soil);

7

- 10 days (Observed DT 50 ) in Soil 2 : Collamer silt loam soil, NY (29% sand, 61% silt, 10% clay, pH 6.1, 2.1% organic carbon, and CEC of 13 meq/100g soil ( Soil 2 );

1 day (Observed DT 50 ) in Soil 3: a German loamy sand soil (44% sand, 512% silt, 4% clay, pH 6.1, 2.9% organic carbon, and CEC of 9 meq/100g soil ( Soil 3 ); and

In Hours (Observed DT 50 ) in Soil 4: a German loam soil (11% sand, 72% silt 17% clay, pH 7.1, 1.0% organic carbon, and CEC of 13 meq/100g soil ( Soil 4 ); and

Metiram residues

Soil 1 (Cashmere LS soil) : Quantification of residues is questionable 2 ; Degradates: Transient Species (TDIT+EBIS +Carbimid): Max 16% @ zero d then declined to <1% @ 30 d; ETU: 11% @ 2 d then declined to <1% @ EOS;
EU: 3% @ 3 d then sharply declined to <<1% @ 7 d; Un

identified ( UN

- ID consisting of many degradates): 11.6% @ 1 d then declined sharply to 1% at day 240

Un

- extracted Residues (UER): Max with Me

- OH 59

- 67% @ 0

- 30 d (include parent as parent is not extracted by M e

- OH) declined to 38% @ EOS; noting that Max
after double extra ction with Me

- OH and EDTA was 48%
@ 14 d then declined to 32% @ EOS Mineralization to CO 2 : Max 40.8% @ EOS

Soil 2 (NY Collamer SL soil; 59 d study= EOS) : Quantification of residues is questionable 3 ; Identified degradates include: DIDT (EBIS), ETU, EU, UN

- ID,
CO 2 (11% @ EOS) and UER ( 68 to 90% during the study);

Soil 3 & 4 (German LS and L soils; 365 d study): Quantification of residues is questionable 4 ; Identified degradates include: EBIS, ETU, UN

- ID and CO 2 ( 42

- 43% @ EOS ) and UER (Max 82% @ 7

- 14 d declined to
50

- 53% @ EOS ) Soil 1 365 d study)
459069

- 01 (S) &
454394

- 01 (NMR Spectra)

Soil 2 (59 d study)
451452

- 03 (S)

Soils 3 and 4 (365 d study)
001552

- 88 (S)

Anaerobic soil Soils used were the same two German soils used in the
aerobic study: Data suggest that anaerobic metabolism of metiram in both soils, after 30 days aerobic aging was slightly reduced in comparison to aerobic metabolism with identical degradates Soils 3 and 4
001552

- 88 (S)

### 16 Property Value for Metiram Parent & Residues MRID Reference 1

Aerobic Aquatic t 1⁄2 @ 20 o C (100 day study; noting that the sediment was anaerobic) 0.5 days (Observed DT 50 ) in a water/loamy sand sediment from a small stream in Germany (water: pH 7.6, total organic carbon 3.1 mg/L ; sediment: pH=7.0 and O.C= 0.6%); and

0.9 days (Observed DT 50 ) in a water/loamy sand sediment from a pond in Germany (water: pH 8.4, total organic carbon 11.4 mg/L ; sediment: pH=8.3 and O.C= 0.52)

River System Degradates: EBIS: Max 17% @ 2 d then declined <1% at 14 d; ETU: 49% @ 7 d then declined to 19% @ EOS;
EU: 3

- 6% throughout the study; Un

- identified ( UN

- ID consisting of degradates <5% each): 2

- 31% @ 0

- 30 d
then declined to 2% @ EOS

Un

- extracted Residues (UER): Max 31% @ 30 d then
declined to 26% @ EOS Mineralization to CO 2 : Max 33% @ EOS

Pond System Degradates : EBIS: Max 7% @ zero d then declined <1% at 7 d; ETU: 65% @ 1 d then declined to 47% @ EOS;
EU: 1

- 7% throughout the study; Un

- identified ( UN

- ID consisting of degradates <5% each): 2

- 10% @ 0

- 2 d then
declined to 2% @ EOS

Un

- extracted Residues (UER): Max 26

- 27% @ 30 d to
EOS Mineralization to CO 2 : Max 8% @ EOS 459334

- 01 (A) Anaerobic Aquatic t 1⁄2 @ 25 o C No acceptable study

1 Study Classification: A= Acceptable and S= Supplemental ;

2 Quantification of residues is questionable because quantification was executed for Me

- OH extract only. Degradation products in the significant EDTA extract was not identified/quantified;

3 Quantification of residues is questionable because quantification was not one of the objectives of the study and suspected conversion of metiram into these degradates during extraction;

4 Quantification of residues is questionable because TLC were used.



### Data in Table 6 suggest that [ 14 

### C] m etiram parent degraded with in 1 to 7 days under aerobic soil conditions noting that the actual half

- life may be lower due to the fact that metiram parent was determined by CS 2 5



### . Aerobic soil studies appear to demonstrate the effect of the following processes on the polymeric chains of m etiram :

5 In reviews for submitted studies for EBDC fungicides, EFED noted that CS 2 is not specific for metiram determination in systems that include EBDC residues in which sulfur is present in their structure such as EBIS, DIDT and ETU. Additionally, sulfur may also be present in soil/sediment organic matter. Therefore, in presence of s oil/sediment and sulfur containing transformation products, the concentration of the parent will be overestimated resulting in longer
half

- lives for the parent. In fact, the influence of CS 2 forming compound on metiram determination was acknowledged
for st ructures containing two sulfur atoms bound to the same carbon atom such as EBIS (MRID 459069

- 01).

### 17 • D ecomposition /hydrolysis of the polymer chains of m eti ram , by water

, into EBDC ions ; and

t ransformation of the EBDC ions into a residue containing several degradation products by
h ydrolysis/biotransformation ;

• F ormation of substantial amounts of un

- ident ified/un

- extracted residue (UER ) ; and

• Mineralization of the m etiram residues into CO 2



### .

The process of decomposition/hydrolysis appears to s tart in the step of preparing the stock solution
of m etiram polymer as indicated by observation of transformation products at time zero

. Hydrolysis/biotra nsformation appear to cause transformation of the EBDC units into the m etiram
residues consisting of the following major /minor transformation products: EBIS

, TDIT, ET U

, EU

, Carbimid and un

- identified degradates

. P artitioning of significant amounts of the m etiram residues
into the soil resulted in the formation of substantial amounts of an UER

. Finally, mineralization of part of the m etiram residues resulted in production of CO 2



### .

Observed decomposition/degradation in two aerobic water/sediment systems were similar to that
observed in the soil systems. It appears that p rocesses involved in these systems are similar to
those suggested earlier for the aerobic soil systems. In the two systems, p arent decomposes rapidly (within a day ) with the formation of the m etiram residues consisting of the following degradates : EBIS ( with minor TDIT ) , ETU, EU

, UER and CO 2



### .

(c) Mobility

Data for mobility were estimated from a supplemental leaching study ( Table 7 )

. C alculations were based on radioactivity adsorbed to the soils used in these two studies. This is because m etiram degraded very quickly forming the m etiram residues . Therefore, calculated Koc values are for

m etiram residues. Average adso rption coefficient data suggest that the m etiram residues as a
whole are expected to be moderately mobile. This determination may be applied to the metiram
residues as a whole and chemicals in these residues may vary in mobility. Furthermore,
d etermined Koc values were positively correlated to percent clay, percent organic carbon

, and cation exchange capacity suggesting that, at least part of the residues, have affinity for adsorption to the clay and organic matter fractions of the soil.

Table 7 Summary of the transport properties for the m etiram residues

Property Value for Metiram Parent & Residues MRID Reference 1

Adsorption Coefficient (Koc) (Leaching study) 111 mL/g for a Sandy soil from MD (O.M= 0.9%, pH=
6.5 and CEC= 2 meq/100g);

578 mL/g for a Sandy loam soil from CA (O.M= 0.5 %, pH= 6.5 and CEC= 5 meq/100g); 1,061 mL/g for a S ilt loam soil from MS (O.M= 1.0 %, pH= 7.5 and CEC= 10 meq/100g); and 1,738 mL/g for a Clay s oil from M D (O.M= 4.8 %, pH=
5.9 and CEC= 24 meq/100g) 405763

- 01 (S) Average value 872 mL/g Range of values 111

- 1,738 mL/g

Study Classification: S= Supplemental

### 18 (d) Field Dissipation

In a study conducted in upstate New York on sugar

- beets, metiram (applied as Polyram 80WP) dissipated with a DT 50 

### of 143 days while a study conducted in California on the same crop reported

a DT 50 

### of 20 days 

## (MRID s 414408

- 01/02). For the same studies, reported a DT 50 

### s for ETU were
45 and 16 days, respectively. Data on vertical downwards movement of metiram and ETU was limited by the low sensitivity of the analytical method (LOD of 0.05 and 0.01 ppm, respectively). Other major deficiencies of the studies were inadequate storage stability data and possible contamination of samples, which posed further questions about the validity of the se s tudies. No

new terrestrial field dissipation (TFD) study is requested as it would not add to already submitted monitoring studies for ETU.

(e) Bio

- concentration

Data requirement s were waived for metiram because the Kow, is below 100. At such a low Kow, bio

- concentration is not expected to occur in aquatic organisms such as fish.

(f) Transformation Products

Metiram polymer reaching soil (directly and by wash

- off) and aquatic systems (by drift) is expected to decompose /hydrolyze/bio

- transform rather quickly in the water present in these
systems. Initial p roducts are expected to include negatively charged monomeric EBDC units and positively charged Zn ions. Monomeric EBDC units are expected to be highly vulnerable to abiotic hydrolysis and biot ransformation resulting in the formation of the intermediate transformation product EBIS , Carbimid and TDIT . With time, the intermediate products appears to degrade rather quickly into ETU that appears to degrade into EU and other un

- identified chemical species (UN

ID) . In the presence of a solid phase such as soil/sediment and organic matter particles, substantial part of this residue is expected to partition into the soil phase and become un

- extract ed (UER).

Data also show that part(s) of the m etiram re sidues are expected to be mineralized into CO 2 

### ( Figure 2 ).

### 19 Figure 2 Transformation profile for m etiram in soil and aquatic systems (refer to abbreviations below).

EBDC anion + Zn +2



### EBIS (DIDT); Carbimid and TDIT , respectively ( Transitional Degradate s )



## NH

NH C S 

## NH

NH C O

ETU + EU + UN

- ID + UER

Metiram Residues

CO 2

· EBIS= Ethylene bis isothiocyanate sul fide (5,6

- Dihydro

- 3H

- imidazol(2,1

- C)

- 1,2,4

- dithiazole

- 3

- thione ;

· ETU= Ethylene thio urea (2

- Imidazolidinethione) ; CH 3 H 6 N 2 S ; CAS No.: 96

- 45

- 7; Mol. Wt. : 102.16 g mole

- 1

· EU= Ethylene urea (2

- Imidazolidinone) ; CH 3 H 6 N 2 O ; CAS No.: 120

- 93

- 4; Mol. Wt. : 86.09 g mole

- 1

TDIT = 2,3,7,8

- tetrahydrodiimidazo[2,1

- b: 1,2

- e][1,3,5]thiadiazine

- 5

- thione

· UN

- ID= un

- identified degradates;

· UER= Un

- extracted/Unidentified Residue 

### N C

N H

H S -



### N C S - 

### N

N

S N C S C S 

### NH



## S N C

C

NH 2 

### S

N

C C

C N N

S S

N 

## M etiram Polymer

Hydrolysis/biotransformation (Within a day)

Hydrolysis/biotransformation ( Within hours to 10 days d in soil and <1 day in water/sediment systems)

### 20 Figure 3 contains a summary of the observed degradates and UER in two aerobic soil system s

.

Figure 3 Observed extractable/un

- extractable (UER) radioactivity in two soil systems (in percent of the applied radioactivity as parent equivalent with dotted line representing the average)

In the se system s , a suite of degradates (E B I S, ETU, EU and unidentified degradates ; represented by the extractable radioactivity ) form s and reach es maximum of nearly 45

- 62% of the applied rather quickly (within one day)

. Following this maximum

, within a week , a sharp decline of this
suite follows to reach levels of <5% of the applied parent. The sharp decline of the degradate suite appears to coincide with the formation of relatively persistent un

- identified/un

- extracted residues (UER)

. The UER reaches a maximum of nearly 62

- 85 % of the applied within one week and stays nearly s table to the end of the study ( Figure 3 ). It is not possible to construct the formation/degradation profile of the various constituents of the observed degradate suite due to problems related to uncertainties associated with quantification of these degrada tes

.

In another soil system, quantification of degradates was nearly acceptable and the results are
summarized in Figure 4 for the total degradates and UER. In this experiment, two extractions were
used Me

- OH for which degradation products were analyzed. However, a second extraction with EDTA was executed but extracts were not analyzed. The reason given for not characterizing the EDTA extracted residues was the unexpected presence of polymeric metiram but this does not eliminate the possible presence of other degradates. Therefore, the level /identity of degradates

, determined in this study, might is underestimated. The levels of the UER are represented by the

two top line s in Figure 4 . For example The UER level of the UER at day 14 is 63% after MeOH
extraction and is reduced 48% because the additional 15% (63

- 48%) of the UER being extracted by EDTA ( Figure 4 ). 0 10 20 30 40 50 60 70 80 90

0 50 100 150 200 250 300 350 400% of Applied Radioactivity



### Time in Days Extractable-LS Extractable-L Average-Extractable UER-LS

UER-LS Average-UER

### 21 Figure 4 Observed total extractable degradates of metiram in an aerobic soil and the formation
of UER

Again, the sharp decline of the total degradates was followed by the formation of the UER.

Figure 5 contains a summary for the formation and decline of the major degradates of metiram in
this soil. 0 10 20 30 40 50 60 70

0 5 10 15 20 25 30% of Applied Radioactivity



### Time in Days (shown up to 30 days out of 365 days) UER After MeOH + EDTA Extraction: Max 48% Declines to 32% @ 365 days

Total MeOH + EDTA Extract: Max 69% Declines to 7% @ 365 days

Total MeOH Extract: Max 32% Declines to <1% @ 365 days Total EDTA Extract: Max 45% Declines to 6% @ 365 days U ER After MeOH Extraction : Max 67% Declines slowly to 38% @ 365 days

### 22 Figure 5 Formation and decline of the major transient degradates and other degradates forming
in the aerobic soil

Data in Figure 5 suggest the following:

(a) Transient species TDIT, EBIS and Carbimid “CARB” forms immediately following application to the soil with a half

- life ( from maximum formation ) of < 1 day

. The transient species are dominated by TDIT. Similarly, the UN

- ID degradates form just at the same
time and reach maximum formation within one day following a sharp decline to nearly 5%
within a week and cont inues to decline ; and

(b) ETU and EU degradates reach their maximum within two and three days (just after the sharp decline of transient species ) suggesting their formation from these species. T he
maximums for these two degradates occ ur consecutively at 1 da y for ETU then at 2 days
for EU , their level of formation were different ( ETU maximum 11 % of the applied while

EU maximum 3% of the applied). Both degradates appear to degrade with very short half

lives (0.2 day)

.

Figure 6 contains a summary of the observed total degradates and UER in two aerobic water/
anaerobic sediment soil system s

. Max TRANS 15.7 %

Max ETU 11%

Max EU 3 % Max UN

- ID 11.6 %

0 2 4 6 8 10 12 14 16

0 1 2 3 4 5 6 7 8 9 10% of Applied Radioactivity

Time in Days



### Transient Degradates (TRANS) ETU EU UN-ID

### 23 Figure 6 Observed degradates and UER in two aerobic water/anaerobic sediment systems

In the aerobic water/ anaerobic sediment systems, a suite of degradates ( EBIS , ETU, EU

, and unidentified degradates) forms and reaches maximum of nearly 80 % of the applied rather quickly (within one day ). Following this maximum

, a gradual decline of this suite continues to reach levels
of 54

- 58% of the applied parent in the pond system and 25 % in the river system . The gradual decline of the degradate suite appears to coincide with the formation of relatively persistent un

identified/un

- extracted residues (UER). The UE R reaches a maximum of nearly 30% of the applied
within one month and declines slowly to nearly 25% at 100 days “end of study” ( Figure 6 ). It is noted that formation levels of the UER with time were the same in both pond and river system.

Figure 7 shows the formation/degradation pro file of the various constituents of the observed degradate suite in the water/sediment system s

. 0 10 20 30 40 50 60 70 80

0 10 20 30 40 50 60 70 80 90 100% of Applied Radioactivity



### Time in Days Pond: UER River: UER UER Average
Pond: All Degradates River:All Degradates All Degradates Average

### 24 Figure 7 Formation and decline of the major degradates of metiram in two aerobic water/anaerobic sediment systems (The figure represents river/pond averages)

Data in Figure 7 suggest the following:

(a) The transitional degradate EBIS appears to form immediately foll owing application to the water/sediment systems at low levels possibly because it degrades fast to ETU.

(b) ETU appears to be the major degradate in both systems as it forms/reach its maximum
formation ( of 54

- 65% of the applied ) within a day. Following m axim um, ETU degrades relatively slowly to reach 18 and 47% in the river and pond systems, respectively, at the
end of the 100

- day study. Estimated single 1 st 

### order half

- life is 71 days in the river system
and 264 days in the pond system. ETU degradation patter n i s similar in timing/intensity to
evolved CO 2 

### suggesting bio

- degrad ation by mineralization;

(c) EU appears to be maintained at a level of 4

- 6% throughout the stud y ; and

(d) UN

- ID a ppears to reach a maximum of 11% at days 1 to 2 then degrades to a level of 1.8% by the end of the 100 day study. Estimated half

- life for these unknowns is 16 days.



## 5.2 **The Major**  **Metiram Degradate**  **: Ethylenethiourea (ETU)** 

ETU is a common metabolite/degradate of the EBD C fungicides (EBDCs) including m etiram . As

a m etiram degradate, ETU can be anticipated to be found wherever this fungicide is used. In an agricultural setting, ETU is introduced into the environment in three ways following application
of m etiram fungicide. First , ETU may be added with the applied formulation as it may form in these formulations as a result of particle size reduction ( i.e.

, colloidal milling) and/or due to unfavorable storage ( In EBDCs, up to 13% of the active ingredient was foun d to be converted to ETU). Second , ETU is produced from hydrolytic/biotic degradation of parent m etiram following ETU Max 59.3 % (53.8% in the River system and 64.7% in the pond system)

0 10 20 30 40 50 60

0 1 2 3 4 5 6 7% of Applied Radioactivity



### Time in Days EBIS ETU EU UN-ID

### 25 its application to soils and/or after reaching water bodies by drift. Third , ETU may be produced from further hydrolysis/biotransformation o f transient species in pore water/water bodies and possibly from soil/sediment bound residue of m etiram

. Rapid hydrolysis/biotransformation of

m etiram parent and/or residues are expected to be t he major processes that control ETU production
in soils and w ater bodies. In addition, slow biotic degradation of un

- extracted (UER) m etiram
residue s may also contribute to the production of ETU in the long term. It is noted that the slow production of ETU from m etiram UER is uncertain as the identity of these resi dues are unknown.

As stated above, ETU is produced mainly from decomposition/ hydrolytic/biotic degradation of
parent m etiram . Laboratory data on hydrolysis of m etiram suggest that hydrolysis may be one of the major processes in ETU production. However, data presented are uncertain as identification of transient species and degradates were obtained from experiments started with concentrations much higher than the solubility limit of metiram and was largely dependent on the TLC methods. Therefore, a new hy drolysis study is requested for m etiram in which all degradation products, including ETU are tracked.

In the aerobic soil system, hydrolytic/biotic degradation of parent m etiram appear to produce ETU. Although data indicates presence of ETU in four soils ( Table 6 ), quantification data are not certain in three of the soils and probably underestimated in the fourth soil. In this soil, observed maximum

was 4.2% ( 11.2% of the applied radioactivity in parent equivalent) at day 2 which was followed by sharp dec line to <LOQ at day 14. This data is summarized in Figure 8.

Figure 8 Formation and decline of ETU in a m etiram aerobic soil study ( Collamer soil , ID)

Similarly ETU was observed to be produced in the aerobic aquatic systems from hydrolytic/biotic degradation of parent m etiram . In these systems, maximum s observed was range d from 18

- 23 % ( 47

- 61 % as parent equivalent) ( Figure 9 ) 0 1 2 3 4 5

0 2 4 6 8 10 12 14 16% ETU



### Time in Days

### 26 Figure 9 Formation and decline of ETU in a metiram aerobic aquatic study (two systems)

Finally, ETU may also be introduced to the environment from its extensive use as accelerator in synthetic rubber production and as vulcanizing agent in some poly

- ethers product ion.
Environmental contamination from these industrial uses are not within the FIFRA statutory
framework and to will not be covered by the future risk assessment.

(a) Physical/Chemical and Abiotic Transformation

The chemical structure, physical/chemical characteristics and abiotic transformation of ETU are
summarized in Table 8

.

Table 8 Chemical structure, physical/chemical characteristics and abiotic transformation of ETU 0 5 10 15 20 25

0 20 40 60 80 100% ETU



### Time in Days River: ETU Pond: ETU Average: ETU

Property Value Reference

Identity/Structure CAS Number (Name): 96

- 45

- 7 (2

- Imidazolidinethione) Molecular Weight ( Formula) 102.2 g mole

- 1 (C 3 H 6 N 2 S)

n
- octanol

- Water Coefficient (K OW ) 0.2 MRID 406510

- 01 (A) 1 Vapor Pressure 5.01x10

- 3 torr Neely WB & Blau GE 2

Henry's Law constant 3.4X10

- 7 atm. m 3 mole

- 1 Meylan WM & Howard

PH 3 Water Solubility 20,000 ppm @ 20 o C and 90,000 ppm @ 60 o C Product Chemistry Data Hydrolysis half

- life (t 1⁄2) Stable @ 25 o C and pH 5, 7, and 9 MRID 404661

- 03 (A) 1

Aqueous photolysis t 1⁄2 Stable in pH 7 buffered water ( Ross and Crosby 3 reported
that the Maximum ETU absorb ance lies at 240 nm) MRID 404661

- 02 (A) 1

Soil photolysis t 1⁄2 Stable (Based on Data and UV/Visible spectra) MRID 404661

- 01(A) 1

1 Study Classification: A= Acceptable; S= Supplemental

2 Neely WB and Blau GE 1985. Environmental Exposure from Chemicals. Boca Raton, FL: CRC Press pp. 31

3 Meylan WM & Howard PH 1991. Environ Toxicol Chem 10: 1283

- 93 (Fragment constant estimation method) 

### NH

NH C S

### 27 Data in Table 8 indicate that ETU is a low molecular

- weight chemical that is highly soluble in water. The high vapor pressure of ETU suggests partitioning into the air can be an important route of its dissipation in the environment, especially from dry surfaces. The rela tively low Henry’s Law
constant suggests possible low volatilization of ETU into the air from wet soil and water

. ETU has
a low K ow 

### value suggesting that it will not be significantly bio

- concentrated by aquatic organisms
such as fish. Abiotic process such as hydrolysis and photolysis are not expected to be important in dissipation of ETU in the environment.

(b) Biotic Transformation

Fate data for ETU is extracted from parent studies and/or ETU studies were ETU is the test substance. A summary of this data are presented in Table 9

.

Table 9 Summary of environmental fate properties of ETU

Property Value MRID Reference 1

Aerobic soil t 1⁄2 ( ETU study @ 25

o C and End of study (EOS)= 7 day) From Parent Study: Quantification of ETU in the aerobic soil studies are questionable due to reasons stated previously. It is noted that data suggests short half

- lives for ETU in the aerobic soil system

From ETU Study: 1.6 days in Collamer silt loam soil from Wayne Co., NY; pH= 6.1, organic matter= 3.6% and CEC= 13 meq/100g;
and 1.4 days in Oakville sand soil from Wayne Co., NY; pH= 6.8, organic matter= 2.1% and CEC= 6 meq/100g;

Note: t 1⁄2= 3.2 days was observed in Collamer silt loam
soil when soil moisture was reduced from 70 to 40% of the soil water holding capacity Major Degradates: EU was only tracked with Max of 3

- 3.4% @ <1

- 2 days and then declined to <0.2

- 0.3% @
EOS

Un

- extracted Residues (UER); Mineralization to CO 2 and Mass Balance : Not determined Parent Study:
459069

- 01 (S) &
454394

- 01 (NMR Spectra);
451452

- 03 (S) &
001552

- 88 (S)

ETU Study:
452251

- 01 (S) &
451464

- 01 (S)

Aerobic Aquatic t1⁄2 @ 25 o C From Parent Study: 71 days (Single 1 st order) in a water/loamy sand sediment from a small stream in Germany (water: pH 7.6, total organic carbon 3.1 mg/L ; sediment: pH=7.0 and O.C= 0.6%); and

264 days (Single 1 st order) in a water/loamy sand sediment from a pond in Germany (water: pH 8.4, total organic carbon 11.4 mg/L ; sediment: pH=8.3 and O.C= 0.52) From ETU Study: No acceptable study Parent Study:
459334

- 01 (A)

Anaerobic Aquatic t1⁄2 @ 25 o C No acceptable study ; if no study is submitted; ETU will be considered
stable

Study Classification: A= Acceptable and S= Supplemental

### 28 Data in Table 9 suggest the following:

(1) ETU degraded under aerobic soil conditions with a 90 th 

### percentile t1⁄2 of 2 days (n=2). Only EU degradate was tracked and observed at levels ranging from 3

- 3.4% of the applied radioactivity. The study demonstrated vulnerability of ETU to biodegradation in the soil
system . It is impor tant to note that slightly longer 90 th 

### percentile t1⁄2 of 12 days (n=5) was
observed when the estimated half

- lives of ETU from mancozeb studies was included in the
calculation.

(2) E TU degraded under aerobic water/anaerobic sediment systems with a single 1 st 

### or der half

- life
of 71 days in the river system and a single 1 st 

### order half

- life of 264 days in the pond system.

(3) Observed half

- lives of ETU in the soil system are much shorter than those observed in the water/sediment systems.

Due to deficiencies in submitted anaerobic aquatic studies, ETU will be considered stable unless a new study is submitted that indicates otherwise. In requested studies, ETU and degradates should
be tracked with the latest available analytical procedures. In addition, extraction method should prove to be appropriate as per EFED un

- extracted residues guidance 6



### .

(c) Mobility

Data for mobility were estimated from a supplemental adsorption/desorption study ( Table 1 0 ). It is noted that there were problems with th is study such as the possibility of occurrence of degradation of ETU before conducting the e xperiment . The study was classified as supplemental following registrant submittal of data suggesting that the applied test substance included significant quantitie s of ETU.

Table 10 Summary of the transport properties for ETU

Property Value for Metiram Parent & Residues MRID Reference 1

Adsorption Coefficient (Koc) (Adsorption/desorption study) 150 mL/g for a Sandy soil from GA (O.M= 0.9 %, pH=
5.7 and CEC= 4 meq/100g);
57 mL/g for a Sandy loam soil from GA (O.M= 2.8%, pH= 5.9 and CEC= 6 meq/100g);
42 mL/g for a Silt loam soil from PA (O.M= 3.5%, pH= 6.4 and CEC= 10 meq/100g); and
34 mL/g for a Clay loam soil from MS (O.M= 2.5%, pH= 7.4 and CEC= 13 meq/100g) 002588

- 96 (S)
And
000971

- 58 (S) Average value 71 mL/g Range of values 34

- 150 mL/g

Study Classification: S= Supplemental 

### Based on data presented in Table 11 , ETU is expected to be highly mobile in most soils (Average

K oc 

### = 72 mL/g).

6 URL: http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/environmental_fate_tech_team/Unextrac ted_Residues_in_Lab_Studies.htm

### 29 (d) Field Dissipation

Dissipation half

- lives ( DT 50 

### s) of 1 to 6 days and <7 days were observed in fine sand and silt loam
field soils in parent metiram studies (Supplemental stud ies : Accession No s

. 00 2552

- 29 and
000889

- 23).

(e) Bio

- concentration

ETU is associated with very low K OW 

### values of 2. Fish bioaccumulation study was previously
waived for ETU based on the expected low bio

- concentration as indicated from K OW.



### (f) Transformation Products

ETU is a result of abiotic/biotic degradation of m etiram /m etira m residues reaching soil directly and by wash

- off and reaching aquatic systems by drift. ETU itself is not expected to be affected by hydrolysis/direct photolysis in soils or aquatic systems. In contrast, ETU is expected to be highly affected by aerobic bi odegradation in soils and to a lesser extent in biologically active aquatic media. M any degradation products were thought to be forming as a result of ETU degradation such as EU (2

- Imidazolidone; CAS No. 107

- 15

- 3); HYD or Glycolylurea ( 2,4

- (3H,5H)

- Imidazol edione; CAS No. 461

- 72

- 3); IMID (2

- Imidazoline; CAS No. 504

- 75

- 6); GLY (Glycine= Amino acetic acid; CAS No. 56

- 40

- 6); J.B

. (Jaffe’s Base=1

- (4,5

- Dihydro

- 1H

- imidazol

2

- yl)

- imidazolidin

- 2

- thion; CAS No. 484

- 92

- 4 ); EDA (Ethylenediamine) and CO 2



### . However, only
EU and HYD were confirmed when the results of the TLC method are considered not reliable due to problems stated earlier. The degradation products of ETU will be corrected based on the results of requested new studies.



## 5.3 **Determination of the Stressor of Conc ern for Ecological Risk** 
**Assessment**

Chemical species intensity and timing of exposure and toxicity are used to determine the stressor of concern for the future ecological risk assessment.

Exposure

In the soil system, metiram reaching the soil indirectly upon application and later from wash

- off is expected to degrade into multi chemical species or the metiram residues. The timeline for the change in the chemical species of the metiram residues in the soil is summarized in Figure 9

.

### 30 Figure 9 Expected relative changes in the chemical constituents of the metiram residues with time in the aerobic soil system ( Parent was determined separately by CS 2 

### )

Data in Figure 9 suggest that chemical species that may reach aquatic syste ms by run

- off from the soil include significant amounts of the UER and less e r amounts of ETU, EU and UN

- ID degradates.

In contrast, metiram reaching aquatic systems by drift, is expected to also degrade into the metiram residues producing similar chemic al species with different concentrations and at different time

line as shown in Figure 10 , below.

Figure 1 0 Expected relative changes in the chemical constituents of the metiram residues with time in aerobic aquatic systems (Average of two systems) 0% 20% 40% 60% 80% 100%

0 1 2 3 7 14 30 62 90 121 240 365% OF APPLIED RADIOACTIVITY



### TIME IN DAYS

Transient Degradates (TRANS) ETU EU UN-ID UER CO2

0% 20% 40% 60% 80% 100%



### 0 1 2 7 14 30 62 100% OF APPLIED RADIOACTIVITY



### TIME IN DAYS



### Parent EBIS ETU EU UN-ID UER CO2

### 31 Data in Figure 1 0 suggest that the constituents of the m etiram residues will be dominated with un

degraded parent from drift alone

, transient species ( EBIS , Carb imid and TDIT), ETU and EU at the short term and EU and the UER at the long term . Therefore, aq uatic exposure will be associated
with un

- degraded parent from drift alone

, transient species ( EBIS , Carbimid and TDIT )

, ETU and EU at the short term and the UER and EU at the long term.

Toxicity

The toxicity of the transient species (EBIS, Carbimid and TDIT) and major degradates: ETU, EU and UER is considered hereafter to decide which of these degradates may be included in the

stressor.

As noted above, there is a relatively robust data set available to characterize the acute and chronic toxicity of ETU to aquatic taxa. These data are further discussed in Section 5 of this assessment. A comparatively smaller dataset exists for EU and only for acute exposure. These data are
summarized in Table 1 1 below alongside the endpoints derived from parent metiram studies. For the transient degradate EBIS, there is no registrant submitted data available, and therefore t he structural activity relationship (SAR) tool ECOSAR (v 1.1) was employed to estimate the toxicity

to taxa w here no data are available. The results below indicate that for taxa for which registrant
submitted studies are available for as well as ECOSAR estimates for where there are gaps in the dataset for EU, that ETU and EU are generally at least two order s of magnitude less toxic than parent metiram

. As shown in Table 1 1 , the transient degradate EBIS is estimated to elicit toxicity similar to that of parent metiram and for some taxa, is estimated to be more toxic than parent
metiram.

Table 11

. Summary of r egistrant s ubmitted and ECOSAR estimates of the various degradation product of metiram

Taxa 

Stressor (data source) FW Fish
LC 50 FW
Invert
LC 50 FW fish
NOAEC FW invert
NOAEC E/M
fish
LC 50 E/M
invert
LC 50 E/M Fish
NOAEC FW
Green Algae

Parent m etiram (registrant submitted data) 0.23 0.63 0.07 Study in
review >0.67 0.025 0.015

ETU (registrant submitted data) >502 26.9 Study in
review >895 7.8 23

EU (registrant submitted data) >122 985 119

EU (Substituted ureas ECOSAR class) 2735 8624 5.57 204 94.2 1351 4.07 156

EU (Amides ECOSAR class) 7183 855 22.7 272 17.6 1428 21.6

E BIS (Thiocarbamate, di (substitute ECOSAR class) 0. 18 0.62 0.015 ** 0.041 ** 0.1 0

### 32 Taxa 

Stressor (data source) FW Fish
LC 50 FW
Invert
LC 50 FW fish
NOAEC FW invert
NOAEC E/M
fish
LC 50 E/M
invert
LC 50 E/M Fish
NOAEC FW
Green Algae
Carbimid (Imide ECOSAR class) 231 5.4 12.6 44.4 277 17322 13 0.08

Carbimid (Thioureas ECOSAR class) 370000 * 14.9 24389 1 1.36 ** 10.1

TDIT (Thioureas ECOSAR Class) 999 2.93 114 0.14 ** 1.38

*Indicates the chemical may not be soluble enough to measure this predicted effect.

** Indicates this endpoint was estimated using an acute

- to

- chronic ratio (ACR)

.



### As shown in Figure 10 above, upon entering the water column, metiram shows a rapid
transformation within 1 day to ETU, at which point the relative concentration of parent remaining is approximately 25 % , compared to approximately 60% for ETU . This decomposition continues whereby after 2 day s , total parent metiram is approximately 13% w hile ETU and EU residues make up a combined 65 %. The un

- extracted residues, along with EU, comprise the majority of residues in the water/sediment system after 30 day s (70%). The toxicity of the un

- extracted residues is uncertain, however for mancozeb, another EBDC chemical, sub

- chronic 10

- day studies of parent mancozeb compared to the un

- extracted residues show increased toxicity of the un

extracted residues by approximately an order of magnitude. Sub

- chronic (10

- day) studies conducted with parent metiram on the freshwater midge and estuarine/marine amphipod are currently in review. These data will not address the uncertainty of the extent of toxicity of the un

extracted residues but in the absence of such information, increased toxicity of the un

- extracted residues will be assumed based on the data available for mancozeb. While the toxicity of the se

un

- extracted residues to other aquatic taxa, including water column organisms, is uncertain, the
extent to which the un

- extracted residues would be bioavailable these organisms is expected to be low. More likely, these pelagic organisms would be exposed to relatively stable concentrations of
ETU and EU which regist rant submitted studies show to be less toxic than parent metiram on an acute basis and ECOSAR estimates show to be less toxic than metiram on a chronic exposure basis

In contrast, the drinking water stressor is ETU, the major degradate of metiram forming in aquatic systems from drifted parent and ETU that forms in the soil and transported to these systems by

run

- off.

What follows is a summarization of the ecological stressor of concern for each taxa:

Ecological stressor of concern (aquatic orga nisms):

• The total residues of un

- degraded metiram parent plus the transient species EBIS
, Carbimid, and TDIT for acute exposure: the source of metiram parent and EBIS , Carbimid,
and TDIT is expected to be from drifted parent alone as metiram reaching the soil system and resultant transient species ( i.e. , EBIS) and degradates ETU and EU forming in the soil are not expected to reach aquatic systems by run

- off because they are short lived. Additionally, it is
noted that at most (per Figure 10 ), EU is 27X less acutely toxic than parent (based on

### 33 freshwater invertebrate data), and at Day 1, EU is present at about 2.5X that of parent, so its contribution to overall toxicity would be very limited.

• For chronic exposure : UER that forms following de gradation of drifted parent and that carried by run

- off from the UER forming in the soil system.

Ecological stressor of concern (terrestrial foliar residues for birds and mammals):

• Parent metiram residues on various food items for both acute and chronic risk noting that this will be conservative because the possible occurrence of degradation by moisture will reduce exposure due to the production of the less toxic degradates ETU and EU. It is also noted that this degradation applies to parent metiram beha vior on soil. It is an uncertainty as
to whether metiram follows a similar dissipation pattern on foliage and therefore it is assumed that, without data to suggest otherwise, these residues would be available for ingestion by avian and mammalian species.

Ecological stressor of concern (terrestrial foliar residues for honey bees):

• The discussion above relating to parent metiram residues on various food items for both
and chronic risk also apply to honey bees via direct contact spray toxicity. As metiram does not exhibit systemic properties, its residues would not be expected to be present in pollen and

nectar.



# 6 R eceptors

As described in the Agency's Overview Document (U.S EPA, 2004), the most sensitive endpoint for each taxonomic group will be used to calculate risk quotients (RQs). Assessment endpoints include direct toxic effects on the survival, reproduction, and growt h of terrestrial and aquatic life as well as indirect effects such as reduction in prey base and/or modification of habitat. Acute and chronic toxicity data from studies submitted by pesticide registrants along with the available open
literature are used to evaluate the potential direct effects of m etiram to the aquatic and terrestrial receptors identified in this section. This includes toxicity data on the technical grade active ingredient, degradates, and when available, formulated products. The open lit erature studies are identified through EPA's ECOTOX database ( http://cfpub.epa.gov/ecotox/ ), which employs a literature search engine for locating chemical toxicity data for aquatic life, terrestrial plants, and
wildlife.



## 6.1 **Effects to Aquatic Organisms**

A summary of the available ecotoxicity information and the incident information for metiram is provided below. Table 12 provides a summary of the taxonomic groups and the surrogate species tested to help understand potential acute and chronic ecological effects of metiram. In addition, the table provides a preliminary overview of the potential a cute toxicity of metiram by providing the acute toxicity classifications.

### 34 There are several acute toxicity studies available to characterize the toxicity of metiram to
freshwater fish. Acute LC 50 

### endpoints range from 0.23 to >160 mg a.i/L, which classif ies metiram as highly toxic to freshwater fish on an acute exposure basis. Clinical signs of toxicity that were observed in the studies included loss of mucus secretion from the anus, convulsions, discoloration, and hyperflexia. In one study wi th the blu egill sunfish, although the LC 50 

### was reported to be >160 mg a.i/L, mean measured concentrations ranged from 49

– 72% of nominal and there was a yellow precipitate observed throughout the course of the study which increased as the test concentration
increas ed. Although no mortality occurred in this study, the results are uncertain given that the test concentrations were all above the reported solubility limit of metiram (2 mg/L) and this study was a static exposure test system. Although no chronic early li fe stage (ELS) studies are available for freshwater fish, a subchronic 28

- day study was conducted with the rainbow trout. Mortality as well as growth (length and weight) measurements were captured but reproductive endpoints were not part of the study desi gn. The subchronic 28

- day NOAEC and LOAEC values determined to be 0.07 and 0.22 mg a.i/L, respectively for effects on mortality, length and weight. This study was not designed to fulfill any current EPA guideline. Currently, there is a freshwater fish e arly life stage study with the fathead minnow (MRID 48246303) is in review.

Available data indicate that metiram has a 96

- hr LC 50 

### of >0.67 mg a.i/L on an acute exposure basis to estuarine/marine fish. There were no reported clinical signs of toxicity dur ing the course of the study. There are no available chronic toxicity studies for estuarine/marine fish.

Acute toxicity data for freshwater invertebrates indicate that metiram is highly toxic, with a 48

- hr
EC 50 

### of 0.63 mg a.i/L. Clinical signs of toxi city included lethargy and trapped at the surface of the tank with pale discoloration. A chronic life cycle study with Daphnia magna exposed to flow
th r ough conditions of metiram has been submitted and is currently in review (MRID 48392001).

Availab le data for characterization of the acute toxicity of metiram to estuarine/marine invertebrates indicate the chemical is very highly toxic on an acute exposure basis with LC 50 

### values ranging from 0.025

– 0.83 mg a.i/L. There were no clinical signs of toxi city noted in either an acute toxicity test with the mysid shrimp or an acute oyster shell deposition study. A chronic life cycle study with mysid shrimp exposed to flow through conditions of metiram has been submitted and is currently in review (MRID 483 92002)

There are 5 studies available to characterize the toxicity of metiram to non

- vascular aquatic plants. The most sensitive species was the freshwater diatom. Due to the study not achieving a definitive NOAEC, EFED policy is to use the EC 05 

### in order to estimate risk to listed aquatic non

- vascular plants. Therefore, the 96

- hr EC 50 

### and EC 05 

### are 0.015 and 0.003 mg a.i/L, respectively.

T 

### able 12

. Summary of the m ost s ensitive e ndpoints from a quatic t oxicity s tudies for m etiram

Taxonomic

Group Study Type

– Test Material Surrogate Species Toxicity Value (all units in

terms of
measured active

ingredient) 2 Acute Toxicity
Classification Source (Classification)

Freshwater fish 1 Acute

- TGAI Rainbow trout ( Oncorhynchus mykiss ) 96

- hr LC 50 : 0.23 mg/L (0.14

– 0.93; 2.23) Highly toxic 435250 0 1 (Acceptable)

### 35 Taxonomic

Group Study Type

– Test Material Surrogate Species Toxicity Value (all units in

terms of
measured active

ingredient) 2 Acute Toxicity
Classification Source (Classification)

Sub

- chronic toxicity

- Formulation Rainbow trout ( Oncorhynchus mykiss ) 28

- day NOAEC: 0.07 mg/L;
LOAEC (survival, length, weight): 0.22 μg/L -- 45933402 (Supplemental)

Early life
stage

- TGAI Fathead minnow ( Pimephales promelas ) Study in review (MRID 48246303)

Freshwater
invertebrates Acute

- TGAI

Water flea ( Daphnia magna ) 48

- hr EC 50 : 0.63 mg/L (0.52

– 1.05; N/A) Highly toxic 48151301 (Acceptable)

Chronic (Life Cycle)

- TGAI Study in review (MRID 48392001)

Estuarine/marine
fish Acute Sheepshead
minnow ( Cyprinodon variegatus ) 96

- hr LC 50 : >0.67 mg/L (N/A; N/A) Highly toxic 3 48151303 (Acceptable)

Estuarine/marine
invertebrates Acute

– TGAI Mysid shrimp ( Americamysis
bahia ) 96

- hr LC 50 : 0.025 mg/L (0.019

– 0.033; 2.64) Very highly
toxic 48151304 (Acceptable)

Acute

- TGAI Eastern oyster ( Crasso s trea virginica 96

- hr EC 50 : 0.083 mg/L (0.037

– 0.19; N/A) Very highly
toxic 48151305 (Acceptable)

Chronic Life Cycle

- TGAI Mysid shrimp ( Americamysis
bahia ) Study in review (MRID 48392002)

Sediment

dwelling
invertebrates Subchronic (10

- day)

s piked
sediment
system

– TGAI Freshwater midge ( Chironomus
dilutus ) Study in review (MRID 48246301)

Subchronic (10

- day) spiked
sediment
system Estuarine/marine amphipod ( Leptocheirus plumulosus ) Study in review (MRID 48246302)

Aquatic plants and algae Non

- vascular

- TGAI Freshwater diatom ( Navicula pelliculo s a ) 96

- hour EC 50 (Biomass): 0.015 mg/L (0.012

– 0.019; N/A)

96

- hr EC 05 : 0.003 μg/L -- 47645918 ( Supplemental )

1 Freshwater fish may be surrogates for aquatic

- phase amphibians.

2 (95% confidence intervals; slope) if available

3 Although indicated as highly toxic based on EPA classification system, it is noted that this endpoint is non

- definitive

### 36 Additionally, there are 9 studies available to characterize the acute and chronic toxicity of the primary degradate of metiram , ETU, to aquatic organisms ( Table 13 ). Acute toxicity studies with freshwater fish and invertebrates, estuarine/ marine fish and invertebrates, and aquatic plants indicate that ETU is generally less toxic than parent metiram by at least an order of magnitude, depending on the taxa.

Table 13

. Summary of e ndpoints from a quatic t oxicity s tudies for the m etiram d egradate ETU

Taxonomic Group (study type) Surrogate Species Toxicity Value (all units in
terms of measured active ingredient) 2 Acute Toxicity
Classification Source (Classification)

Freshwater fish 1 (acute toxicity) Rainbow trout ( Oncorhynchus mykiss ) 96

- hr LC 50 : >502 mg/L (N/A; N/A) Practically

non

- toxic 45910401 (Acceptable)

Bluegill sunfish ( Lepomis

macr ochirus ) 96

- hr LC 50 : >988 mg a.i/L Practically

non

- toxic 47441202 (Acceptable)

Freshwater
invertebrates (acute toxicity) Water flea ( Daphnia magna ) 48

- hr EC 50 : 26.9 mg a.i/L (19.6

– 38.5; 1.92) Slightly toxic 45910402 (Acceptable)

Freshwater
invertebrates (chronic toxicity) Study in review (MRID 46462901)

Estuarine/marine
fish (acute toxicity Sheepshead minnow ( Cyprinodon variegatus ) 96

- hr LC 50 : >895 mg a.i/L (N/A; N/A) Practically

non

- toxic 47441201 (Acceptable)

Estuarine/marine
invertebrates (acute toxicity) Mysid shrimp ( Americamysis
bahia ) 96

- hr LC 50 : 7.8 mg a.i/L (5.1

– 10.9; N/A) Moderately
toxic 47441204 (Acceptable)

Estuarine/marine
invertebrates (acute toxicity) Eastern oyster ( Crassotrea virginica ) 96

- hr >110 mg a.i/L (N/A; N/A) Practically

non

- toxic 47474301 (Acceptable)

Aquatic plants Freshwater green algae ( Pseudokirchneriella subcapitata ) 72

- hr EC 50 (cell density): 23.0 mg a.i/L (N/A; N/A)

72

- hr NOAEC: 5.0 mg a.i/L -- 45910403 (Acceptable)

Duckweed ( Lemna gibba ) 7

- d EC 50 : >960 mg a.i/L

7

- d NOAEC: 230 mg a.i/L

7

- d LOAEC (frond density and growth rate): 480 mg a.i/L -- 47441203

1 Freshwater fish may be surrogates for aquatic

- phase amphibians.

2 (95% confidence intervals; slope) if available



### T here are 3 studies available to characterize the acute toxicity to ETU degradate

, which is ethylene urea (EU) to freshwater fish, invertebrates, and green algae ( Table 14 ). The available acute toxicity study for freshwater fish, while not testing as high as the study with ETU, indicates that EU is practically non

- toxic to fish on an acute exposure basis. For freshwater invertebrates and freshwater green al gae, available data indicate that EU is at least one order of magnitude less toxic as compared to ETU.

### 37 Table 14. Summary of Endpoints from Aquatic Toxicity Studies for the ETU Degradate Ethylene Urea (EU)

Taxonomic Group (study type) Surrogate Species 1 Toxicity Value 1 Acute Toxicity
Classification Source (Classification)

Freshwater fish 2 (acute toxicity) Rainbow trout ( Oncorhynchus mykiss ) 96

- hr LC 50 : >122 mg/L (N/A; N/A) Practically

non

- toxic 46462902 (Acceptable)

Freshwater
invertebrates (acute toxicity) Water flea ( Daphnia magna ) 48

- hr EC 50 : >985 mg/L Practically

non

- toxic 46462903 (Acceptable)

Aquatic plants Freshwater green algae ( Pseudokirchneriella subcapitata ) 96

- hr EC 50 : >119 mg/L

96

- hr NOAEC: 119 mg/L -- 46462904 (Acceptable)

1 Concentrations expressed in terms of mean measured active ingredient

. 2 Freshwater fish may be surrogates for aquatic

- phase amphibians.



## 6.2 **Effects to Terrestrial Organisms**

Available acute and chronic studies to characterize the toxicity of metiram on birds include one avian acute oral study, two sub

- acute dietary studies, and two avian reproduction studies. In an acute oral study conducted with the northern bobwhite quail ( C olinus virginianus , MRID
40656901 ), there were no mortalities o r clinical signs of toxicity observed during the course of the study. The LD 50 

### was determined to be >2250 mg a.i/kg

- bw.

Two avian sub acute dietary toxicity studies are available for metiram

, one each for mallard duck and northern bobwhite quail. The most sensitive species was the bobwhite quail, with an 8

- d LC 50 

### determined to be 3712 mg a.i/kg

- diet. Clinical signs of toxicity in the bobwhite study included wing droop, depression, and labore d respiration at the highest treatment concentration (4640 mg a.i/kg

- diet). Similar effect s were not observed in the mallard duck study.

There are two avian reproduction studies available for metiram, one each with the mallard duck and northern bobwhite quail. The study with the bobwhite quail had several deficiencies including high control mortality and a larger than acceptable incidence of cracked eggs in the control group. These deficiencies limit its use in quantitative risk assessment. In the mallard duck study, dietary exposure of 300 mg a.i/kg

- diet to metiram significantly reduced egg production, mean egg weight, and fertility rate while increasing rate of early embryonic deaths. There were no clinical signs of toxicity noted during the course of the study.

A n acute oral toxicity study with metiram on the Norway rat ( Rattus norvegicus ) (MRID 40497002) indicated that metiram is p ractically non

- toxic to mammals on an acute exposure basis
with an LD 50 

### of >10,000 mg a.i/kg

- bw. In a 3

- generation reproduction study, (MRID 00247214), significant (p<0.05) decreases in parental body weight, reduced food consumption, and reduced mating pe rformance were observed at the highest treatment level (320 ppm). The NOAEC was determined to be 40 ppm.

Tier II seedling emergence and vegetative vigor studies are available for metiram (MRID 47645915 and 47645916, respectively). Both studies tested a range of application rates up to a

### 38 nominal application rate of 3.25 lbs a.i/A. In the seedling emergence study, the most sensitive
monocot was determined to be wheat , based on significant effects to dry w eight. The most sensitive dicot was tomato, base d on significant effects to percent emergence . For wheat, the
NOAEC and EC 25 

### were determined to be 0. 37 and >2.86 lbs a.i/A, respectively. For tomato, the
NOAEC and EC 25 

### was determined to be 0.11 and >2.86 lbs a.i/A. An EC 25 

### value could not be
estimated from the statistical analysis since the model did not converge. This was due to there being a U

- shaped pattern to the response curve in which the middle concentration represented the highest reduction in survival from the negative control. As the study was otherwise scientifically sound, it is conservatively assumed that the 0.11 lbs a.i/A treat ment group (2 nd 

### lowest) is the EC 25 

### as this concentration determined exactly a 25% reduction from the negative control in emergence.

In the vegetative vigor st udy, the most sensitive monocot species was wheat, based on an 8% reduction in height at the lowest level and the most sensitive dicot was lettuce, based on a 12% reduction of height at the lowest treatment level. Percent inhibitions of all endpoints for all species
did not exceed 25% and therefore the monocots and dicot EC 25 

### values were determined to be >3.33
lbs a.i/A (mean measured application rate). Although significant reductions in height were found
in wheat and lettuce at the lowest treatment levels, it is noted that these effects did not follow a
clear dose

- response pattern, with the percent reductions at the highest treatment groups being lower than those at the lowest. Specifically, the percent reductions from the negative control for
wheat height for mean measured groups 0.20, 0.40, 0.84, 1.6, and 3.3 were 7.61, 7.4, 5.1, 7.5, and 4.8%, respectively. Similarly, the percent reductions from control for lettuce for mean measured groups 0.20, 0.40, 0.84, 1.6, and 3.3 were 12, 7.1, 4.7, 9.9, an d 4.9, respectively. The EC 25 

### and
NOAEC values are therefore determined to be >3.3 and 3.3 lbs a.i/A.

A combination acute contact and acute oral toxicity to adult honey bees is currently in review (MRID 49403401).
Table 1 5

. Summary of the Most Sensitive Endpoints from Terrestrial Toxicity Studies for
Metiram

Taxonomic

Group Study Type Surrogate Species Toxicity Value (all units in

terms of
measured

active ingredient) 2,3 Acute Toxicity
Classification Source (Classification)

Birds 1 Acute Oral Bobwhite quail ( Colinus virginianus ) 21

- day LD 50 : >2250 mg/kg

bw Practically

non

- toxic 40656901 (Acceptable)

Subacute dietary Bobwhite quail ( Colinus virginianus ) 8

- d LC 50 : 3712 mg/kg

- diet Slightly toxic 00108004 (Acceptable)

### 39 Taxonomic

Group Study Type Surrogate Species Toxicity Value (all units in

terms of

measured

active ingredient) 2,3 Acute Toxicity
Classification Source (Classification)

Chronic Mallard duck quail ( Anas platyrhynchos ) NOAEC = 50 mg/kg

- diet

L OAEC (reduced egg production,

mean egg weight, fertility rate, increased onset of early embryonic death) = 300

ppm -- 42539102 ( Acceptable )

Mammals Acute Oral Norway rat ( Rattus norvegicus ) 14

- day LD 50

> 10000 mg/kg bw (N/A; N/A) Practically

non

- toxic 40497002 (Acceptable)

Chronic ( 3

- generation reproduction) Norway rat ( Rattus norvegicus ) NOAEC = 40

ppm LOAEC (body weight, food consumption, mating performance) = 320 ppm -- 00247124 (Acceptable)

Insects Acute contact and oral toxicity

- TGAI Honey bee ( Apis mellifera ) Study in review (MRID 49403401)

Terrestrial plants Seedling Emergence (Tier II ) Monocot

– Wheat EC 25 > 2.86
lbs/A
NOAEC (dry weight) = 0.37
lbs /A

-- 47645915 (Acceptable)

Dicot

– Tomato EC 25 : >2.86 lbs
a.i/A
NOAEC (percent emergence) = 0.11 lbs/A

Vegetative Vigor (Tier II) Monocot

- None EC 25 > 3.3 lbs
a.i/A
NOAEC = 3.3
lbs a.i/A 47645916 (Acceptable)

Dicot

- None EC 25 > 3.3 lbs
a.i/A
NOAEC = 3.3
lbs a.i/A

1 Birds represent surrogates for terrestrial

- phase amphibians and reptiles.

2 Concentrations expressed in terms of active ingredient.

3 An N/A under endpoint means that there was not a most sensitive species tested.

### 40 Additionally, there are six studies available to characterize the toxicity of ETU to terrestrial organisms. Two acute oral toxicity studies are available for ETU, one each for the northern bobwhite quail (MRID 48343001) and zebra finch (MRID 48437501). These studies are currently
in review.

In two sub acute dietary toxicity studies with the bobwhite quail and mallard duck (MRIDs 48417801 and 48417802, respectively), ETU did not cause mortality in all treatment concentrations. In the bobwhite quail study, there was a reduction in mean body weight chang e in the three highest treatment concentrations as well as a significant (p<0.05) reduction in mean body weight in the two highest treatment concentrations. In the study with the mallard duck, there was a significant (p<0.05) decrease in mean body weight that was determined at all treatment
concentrations.

There are two chronic avian reproduction studies conducted with ETU on the bobwhite quail (MRID 48819701) and mallard duck (MRID 48819702) that are currently in review.

There are no relevant acute or al toxicity or reproductive toxicity studies available for ETU and
mammals.

Table 16

. Summary of Endpoints from Terrestrial Toxicity Studies for the Metiram Degradate

ETU

Taxonomic Group (study type) Study Type Surrogate Species Toxicity Value (all units in terms
of measured active ingredient) 2,3 Acute Toxicity
Classification Source (Classification)

Birds 1 Acute oral toxicity Bobwhite quail ( Colinus virginianus) Study in review (MRID 48343001)

Zebra finch ( Poephila

guttata ) Study in review (MRID 48437501)

Subacute dietary toxicity Bobwhite quail ( Colinus virginianus) LC 50 > 5620 mg/kg

bw (N/A; N/A) Practically non

toxic 48417801 (Acceptable)

Mallard duck ( Anas platyrhynchos ) LD 50 > 5620 mg/kg

bw (N/A; N/A) Practically non

toxic 48417802 (Acceptable)

Chronic avian reproduction Bobwhite quail ( Colinus virginianus Study in review (MRID 48819701)

Mallard duck ( Anas platyrhynchos ) Study in review (MRID 48817702)

1 Birds represent surrogates for terrestrial

- phase amphibians and reptiles.

2 Range of numbers within parentheses refers to the 95% confidence limit of the point estimate value

3 An N/A under endpoint means that there was not a most sensitive species tested



### .

### 41 

## 6.3 **Ecological Incidents**

The ecological incident information system (EIIS) is an EFED

- maintained database that houses ecological incidents that have been reported to the Agency. When available, EIIS includes date and location of an incident, type and magnitude of effects observed in various species, use(s) of pesticides known o r suspected of contributing to the incident, and results of any chemical residue analysis or other analyses conducted during incident investigation. EIIS incidents are categorized according to the certainty that the incident resulted from pesticide exposu re. The OPP

- maintained Incident Database System (IDS) and the Aggregate Incident Database provide incident counts at the chemical and product level but do not provide the narrative information contained in EIIS. The Avian Incident Monitoring System (AIMS ) is a database administered by the American Bird Conservancy that contains publicly available data on reported avian incidents involving pesticides. Many of the incidents listed in this database are also in the EIIS. Searches of the incident databases

w ere conducted in February, 2014.

A search of the IDS and AIMS databases did not return any reported wildlife incidents for metiram.

A search of the Aggregate Incident Database returned one reported wildlife incident s involving
metiram. The incident wa s categorized as “Wildlife

- Minor.” There was no further narrative
information about the incident available.

A search of EIIS returned one wildlife incident that occurred in Canada in 1999. A fish kill was reported in the Tyron River of Prince Edward Island. River water samples indicate a zin phos

methyl, carbofuran, and residues that are characterized as dithiocarbamates. The incident report ultimately concludes that the azinphos

- methyl residues were “highly probable,” in causing the fish kill with the dithiocarbamate residues as “unlikely.” It is noted that it is not specified in the incident report which dithiocarbamate was suspected as there are several chemicals in this class.

There were no reported wildlife incidents in any of the aforementioned databases for ETU , which
was screened as it is associated with its own PC code and data set

.



# 7 Exposure Pathways of Concern

The environmental fate properties and use patterns of m etiram indicate that direct spray, spray drift, and runoff (mainly in events accompanied by erosion), represent potential transport
mechanisms of m etiram residues to aquatic and terrestrial organisms. Leaching to groundwater is an important pathway for ETU, th e drinking water degradate of concern (ETU)

.

Other Exposure Pathways to Terrestrial Species

Drinking Water Exposure

The S creening I mbibition P rogram (SIP v.l.0), Released June 15, 2010) was used to calculate an upper bound estimate of exposure using metiram’s solubility ( 2 mg/L), the most sensitive acute (mallard duck acute oral LD 50 

### >2150 mg a.i/kg

- bw) and chronic avian toxicity endpoint ( mall ard

### 42 duck NOAEC of 50 ppm) and the most sensitive acute and chronic mammalian toxicity endpoints (Norway rat LD 50 

### of >5000 mg a.i/kg

- bw and Norway rat NOAEL 40 ppm, respectively). Drinking water exposure alone was not determined to be a potential pathwa y of concern for acute and chronic avian and mammalian exposure.

Although drinking water exposure alone does not appear to be of concern, when aggregated with other exposure pathways (dietary food sources, dermal, inhalation), drinking water may cont ribute to a total exposure that has a potential for effects on non

- target animals. Because there is a high degree of conservatism in the SIP 1.0 exposure estimate, there is a limited expectation that use scenarios not triggering a SIP 2.0 concern would con tribute significantly to aggregate risks from water plus diet when a refined water exposure model is incorporated in the actual quantitative risk
assessment. Detailed information about SIP v.l.0 as well as he tool can be found on the EPA's
website at http://www.epa.gov/pesticides/science/models/pg.htm#terrestrial

.

Inhalation Exposure
The S creening T ool for I nhalation R isk (STIR v.l.0, November 19, 2010) was used to calcula te an upper bound estimate of exposure usi ng metiram’s vapor pressure (7.5 0E

- 8 

### torr) and molecular weight (1088 g/mol) for vapor phase exposure as well as the maximum application rate and method of application for spray drift. STIR incorporates results from several toxicity studies including acute oral bird toxicity endpoints (mall ard duck acute oral LD 50 

### = >2150 mg a.i/kg

- bw) acute oral and inhalation rat toxicity endpoints obtained from the "six pack," of core studies for technical and formulated products (rat oral LD 50 

### = >5000 mg a.i/kg

- bw and inhalation LC 50 

### = >5.70 mg/L).

Bas ed on the results of the STIR model, inhalation exposure alone was not determined to be a potential pathway of concern for mammalian species on an acute basis.

Inhalation exposure via spray drift and/or vapor

- phase of metiram alone does not appear to be o f concern. The analysis of the inhalation route in STIR does not consider that aggregation with other exposure pathways such as dietary, dermal, or drinking water may contribute to a total exposure that has a potential for effects to non

- target animals. H owever, the Agency does consider the relative importance of other routes of exposure may be potentially significant contributors to wildlife risk (US EPA, 2004). Detailed information about STIR v.l.0, as well as the tool, can be
found on the EPA's website at: http://www.epa.gov/pesticides/science/models/pg.htm#terrestrial

Dermal exposure

Potential exists for metiram dermal exposure to terrestrial wildlife. At the present time, the Agency does not have a method to quantify levels of dermal exposure from chemical applications, but is actively working on a screening tool to account for this route of exposure.

Exposure resulting from bioaccumulation

Metiram is associated with a K OW 

### value of <100

. While there is no BCF study in fish available,
metiram ’s potential to bioconcentrate in aquatic organisms such as fish is expected to be low.

### 43 

# 8 Analysis Plan

**8.1 Stressors of**  **Concern**

i. Ecological Risk Assessment

Please see the section entitled “ Determination of Metiram Residues of Ecological Concern ” in
Section 5.3 of this assessment for a detailed rationale for identifying the stressor of concern for the registration review ec ological risk assessment

.

ii. Drinking Water

The stressor of concern for drinking water is Ethylenethiourea (ETU , a group B2 carcinogen )

, the common degradate of all Ethylene

- bis

- dithiocarbamates (EBDCs) fungicides including m etiram

.



## 8.2 **Measures of Exposure**

EFED will use the most current accepted models to evaluate potential exposures to aquatic and terrestrial organisms as described at http://www.epa.gov/ pesticides/science/models_db.htm

. Aquatic Exposure EECs will be estimated for the total toxic residues of parent plus EBIS , the stressor for the water column of the aquatic system. Additionally, sediment only EECs for the
UER will be estimated, by modeling , using its observed maximum concentration in the soil system as an application rate and the observed half

- lives to represent degradation.

The Agency is aware of ETU monitoring conducted by the EBDCs Task Force and will consider this data and any other available federal and state agencies data in the future registration review
risk assessment.



## 8.3 **Measures of Effect**

Toxicity data presented in Section 3 of this problem formulation will be used to calculate risk quotients. Any additional information submitted by the registrant or found in the open literature prior to conduct of the risk assessment will also be considered. The open literature studies are
ide ntified using EPA’s ECOTOXicology database ( ECOTOX) , which employs a literature search engine for locating chemical toxicity data for aquatic life, terrestrial plants, and wildlife. The evaluation of both sources of data can also provide insight into the direct and indirect effects of pesticides on biotic communities from loss of species that are sensitive to the chemicals and from changes in structure and functional characteristics of the affected communities.



# 9 Endangered Species Assessments

Consistent w ith EPA’s responsibility under the Endangered Species Act (ESA), the Agency will evaluate risks to federally listed threatened and endangered (listed) species from registered uses of pesticides in accordance with the Joint Interim Approaches developed to i mplement the

### 44 recommendations of the April 2013 National Academy of Sciences (NAS) report, Assessing Risks to Endangered and Threatened Species from Pesticides

. The NAS report outlines recommendations on specific scientific and technical issues related to the development of pesticide risk assessments that EPA and the Services must conduct in connection with their obligations
under the ESA and FIFRA. EPA will address concerns s pecific to metiram in connection with the development of its final registration review decision for metiram

In November 2013, EPA, the U.S. Fish and Wildlife Service, National Marine Fisheries (the Services), and USDA released a white paper containing a summary of their joint Interim Approaches for assessing risks to listed species from pesticides. These Interim Approaches were developed jointly by the agencies in response to the NAS recommendations, and reflect a common approach to risk assessment shar ed by the agencies as a way of addressing scientific differences
between the EPA and the Services. Details of the joint Interim Approaches are contained in the November 1, 2013 white paper

, Interim App roaches for National

- Level Pesticide Endangered Species Act Assessments Based on the Recommendations of the National Academy of Sciences April 2013 Report.

Given that the agencies are continuing to develop and work toward implementation of the Interim

A pproaches to assess the potential risks of pesticides to listed species and their designated critical habitat, this ecological problem formulation supporting the Preliminary Work Plan for metiram does not describe the specific ESA analysis, including effec ts determinations for specific listed species or designated critical habitat, to be conducted during registration review. While the agencies continue to develop a common method for ESA analysis, the planned risk assessment for the registration review of m etiram will describe the level of ESA analysis completed for this particular registration review case. This assessment will allow EPA to focus its future evaluations on the types of species where the potential for effects exists, once the scientific method s being developed by the agencies have been fully vetted. Once the agencies have fully developed and implemented the scientific methods necessary to complete risk assessments for listed species and their designated critical habitats, these methods will be applied to subsequent analyses of metiram as part of completing this registration review.



# 10 Endocrine Disruptor Screening Program

Metiram was not included in the first group of 67 chemicals issued an order to conduct Tier 1
EDSP testing. For additional information on the EDSP program, visit http://www.epa.gov/endo/

.



# 11 Preliminary Identification of Data Gaps

**11.1 Environmental Fate** 

Due to the complex nature of polymeric m etiram and the state of science when some of t he studies were conducted, difficulties were observed in these studies including :

(1) Parent degradation in the preparation steps of parent for the experiments; (2) H igh percentage of the un identified radioactivity remained un extracted in the soil/sediment;

### 45 (3) Methods used for extraction have had degradation effects on polymeric parent and possibly monomeric segments of the parent. For example, extraction in one study appeared to cause some degree of conversion of parent into E TU even in the presence of chemicals that are believed to minimize such effects; (4) Solvents including water appeared to cause hydrolytic decomposition of the polymeric parent
into un identified residue (possibly monomeric species); and (5) Particle size reductio n and presence of metal ions (that may replace zinc ion in the structure) are thought to increase hydrolytic decomposition and degradation rate.

The Agency unders tands difficulties that relate to the nature of the chemical and therefore request only studies that are expected to produce data with less uncertainties giving the advances
in science since these studies were conducted. Tables 17 and 18 identify environmental fate studies by MRID for metiram and its main degradate ETU along with their study classifications. The tables also show where additional data are needed to support the future risk assessment.

Table 17 Submitted environmental fate data for Metiram

OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classification Are data needed to
conduct risk assessment?

835.2120 Hydrolysis 001551

- 89 (S);
001619

- 37 (S);
001467

- 64 (S) Supplemental Yes for Metiram a.i

835.2240 Aqueous photolysis 001551

- 90 (A);
001 619

- 38 (A) Acceptable No

835.2410 Soil photolysis 001570

- 31 (A) Acceptable No

835.4100 Aerobic soil metabolism 459069

- 01 (S) &
454394

- 01 (S);
451452

- 03 (S);
001552

- 88 (S) Supplemental Yes for Metiram a.i

835.4200 Anaerobic soil metabolism No acceptable study No

835.4300 Aerobic aquatic metabolism 459334

- 01 (A) Acceptable No

835.4400 Anaerobic aquatic metabolism No acceptable study Yes for Metiram a.i

835.1230
835.1240 Adsorption/ desorption and leaching 405763

- 01 (S) Supplemental No

835.1410 Volatility

– laboratory No acceptable study No

835.6100 Terrestrial field dissipation 414408

- 01/02 Supplemental No

835.8100 Volatility

- field Not required

850.1730 Fish bio

- concentration Waived because Metiram K
ow 6 to 83 No

850.6100 Environmental chemistry
method in soil /validation (ECM/ILV) None submitted YES

850.6100 Environmental chemistry
method in water/validation (ECM/ILV) None submitted YES



### Table 18 Submitted environmental fate data for Metiram major degradate ETU

OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classification Are data needed to
conduct risk assessment?

835.2120 Hydrolysis 404661

- 03 Acceptable No

835.2240 Aqueous photolysis 404661

- 02 Acceptable No

### 46 OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classification Are data needed to
conduct risk assessment? 835.2410 Soil photolysis 404661

- 01 Acceptable No

835.4100 Aerobic soil metabolism 452251

- 01 &
451464

- 01 Supplemental Yes for ETU
as test substance

835.4200 Anaerobic soil metabolism No acceptable study No

835.4300 Aerobic aquatic metabolism No acceptable study Yes for ETU
as test substance

835.4400 Anaerobic aquatic metabolism No acceptable study Yes for ETU

as test substance

835.1230
835.1240 Adsorption/ desorption and leaching 002588

- 96 &
000971

- 58 Supplemental No

835.1410 Volatility

– laboratory No acceptable study No t at this time

835.6100 Terrestrial field dissipation 00 2552

- 29
And 000889

- 23 Supplemental No

850.1730 Fish bio

- concentration Waived because ETU K
ow 2 No

850.6100 Analytical method in soil (ECM/ILV) None submitted Yes Analytical method in water (ECM/ILV) ECM: 448804

- 01*
ILV: 451514

- 01 Acceptable No

* URL: http://www2.epa.gov/sites/production/files/2014

- 12/documents/448804

- 01

- w.pdf



## 11.2 **Effects**

Tables 19

- 23 identify ecological effects studies by MRID that offer data for each guideline requirement for parent metiram and its major degradation product, ETU in the aquatic media and terrestrial environment, respectively, as well as study classifications and whether or not further
data are needed in order to support risk as sessment. Additionally, available data for the ETU degradate, EU, are provided for aquatic taxa.

Aside from the aquatic studies that are currently in review, there are no identified data gaps for aquatic taxa.

It is noted that there is currently only one study available to characterize the acute oral toxicity of metiram to birds. A preliminary review of an acute oral toxicity study with a passerine species of a related EBDC chemical indicates this chemical class may elicit increased toxicity to passer ine species as compared to the mallard duck and northern bobwhite quail. An acute oral study with a passerine species is recommended to address this uncertainty.

Currently, there are two chronic avian reproduction studies available for metiram. As noted previously, in the study with the bobwhite quail

, several deficiencies including high control mortality and a larger than acceptable incidence of cracked eggs were observed in the control group. These deficiencies limit its use in quantitative risk asses sment. The companion mallard duck study was classified as acceptable. At currently labeled metiram rates and the acceptable chronic NOAEC from the mallard study, chronic avian RQs would reach 55, which is above the
chronic LOC of 1. Despite the fact tha t parent metiram is shown to rapidly degrade to less than 15% parent within a day, these transformation rat e s are derived from soil metabolism studies. It

### 47 is an uncertainty of the behavior of parent metiram when sprayed on foliage as currently labeled

pr actices permit via ground or aerial spray. There is not enough information currently present to assume the degradation rates observed via aerobic soil metabolism pathway would be similar on foliage. Additionally, the bobwhite quail may potentially prove to be the more sensitive species
as it was in the available sub acute dietary studies for metiram. Therefore, an additional avian reproduction study with the northern bobwhite quail is recommended to address this uncertainty.

Please see the discussion ab ove beginning on page 5 of this assessment with regards to the data needs identified relating to honey bees.

Table 1 9

. Submitted Aquatic Ecological Effects Data for Metiram

OCSPP
Guideline Data Requirement Submitted
Studies (MRID) Study
Classifications Are data needed
to conduct risk

assessment? Justification and Assumptions EPA
will Make in
Absence of Data

850.1010 Freshwater
invertebrate acute toxicity 40497003 Invalid

No

-- 43525002 Invalid

44301101 Supplemental

48151301 Acceptable

850.1025
850.1035
850.1045
850.1055 Saltwater
invertebrate acute toxicity 48151304 Acceptable

No

-- 48151305 Acceptable

850.1075 Freshwater fish acute toxicity 40497011 Invalid

No

-- 40945501 Acceptable

43525001 Acceptable

44224401 Invalid

48151302 Acceptable

850.1075 Saltwater fish acute toxicity 48151303 Acceptable No

--

850.1300 Freshwater
invertebrate life cycle 43760402 Invalid

N/A

-- 44301102 Invalid

48392001 Study in review

850.1350 Saltwater
invertebrates life cycle 48392002 Study in review N/A

--

850.1400 Freshwater fish early

- life stage 48246303 Study in review N/A



### --

850.1400 Saltwater fish early

- life stage No data available



### --

850.1500 Fish life cycle

saltwater fish No data available

--

### 48 OCSPP
Guideline Data Requirement Submitted
Studies (MRID) Study
Classifications Are data needed
to conduct risk

assessment? Justification and Assumptions EPA
will Make in
Absence of Data

850.1735 Whole sediment Acute Toxicity Invertebrates,
Freshwater 48246301 Study in review N/A

--

850.1740 Whole sediment: Acute Toxicity Invertebrates,
Marine 48246302 Study in review N/A

--

850.4400 Aquatic plant Toxicity Test using Lemna spp. 45697028 Acceptable No

--

850.4500 Algal toxicity 43199601 Supplemental

No

-- 47645917 Invalid

47645918 Supplemental

47645919 Acceptable

47645920 Acceptable

Non

guideline 28

- day Subchronic Toxicity to
Freshwater Fish 43770401 Invalid

No --

45933402 Supplemental

1 Also known as “Whole Sediment: Subchronic Freshwater Invertebrates,” as per EFED Guidance Document Entitled “Toxicity Testing and Ecological Risk Assessment Guidance for Benthic Invertebrates.” April 2014.

2 Also known as “Whole Sediment: Subchronic Marin e Invertebrates,” as per EFED Guidance Document Entitled “Toxicity Testing and Ecological Risk Assessment Guidance for Benthic Invertebrates.” April 2014.



### Table 20

. Aquatic Ecological Effects Data for ETU

OCSPP
Guideline Data Requirement Submitted Studies (MRID) Study
Classifications Are data needed for risk

assessment ?

850.1010 Freshwater invertebrate acute toxicity 45910402 Acceptable No

850.1025 Saltwater invertebrate acute toxicity 47474301 Study in review N/A

850.1035 Saltwater invertebrate acute toxicity 47441204 Study in review N/A

850.1075 Freshwater fish acute toxicity 45910401 Acceptable No

47441202 Study in review N/A

Saltwater fish acute toxicity 47441201 Study in review N/A

850. 1300 Freshwater invertebrate life cycle 46462901 Study in review N/A

### 49 OCSPP
Guideline Data Requirement Submitted Studies (MRID) Study
Classifications Are data needed for risk

assessment ?

850.4400 Aquatic plant toxicity test using Lemna spp. 47441203 Study in review N/A

850.4500 Algal toxicity 45910403 Supplemental No



### Table 21

. Aquatic Ecological Effects Data for EU

OCSPP
Guideline Data Requirement Submitted Studies (MRID) Study
Classifications Are data needed for risk

assessment ?

850.1075 Freshwater
invertebrate acute toxicity 46462902 Acceptable No

850.1010 Freshwater
invertebrate acute toxicity 46462903 Acceptable No

850.4500 Algal toxicity 46462904 Acceptable No



### Table 2 2

. Submitted Terrestrial Ecological Effects Data for Metiram

OCSPP
Guideline Data Requirement Submitted
Studies (MRID) Study
Classifications Are data
needed for
risk

assessment ? Justification and Assumptions EPA will Make
in Absence of Data

850.2100 Avian oral toxicity

40656901 Acceptable Yes Data are not available for a passerine species . Preliminary review of passerine acute oral study for a related EBDC chemical shows sensitivity of passerine species to this
chemical class

.
850.2200 Avian dietary toxicity 00108004 Acceptable No

-- 00108005 Acceptable

850.2300 Avian reproduction 41082001 Supplemental

Yes Data suitable for quantitative risk assessment are currently only available for one species. Sub acute dietary studies show the more sensitive species to
be the one that chronic data is currently not suitable for. 41156101 Invalid

42539102 Acceptable

850.3020 Honey bee

acute contact
and oral toxicity 49403401 Study in review N/A

--

### 50 OCSPP
Guideline Data Requirement Submitted
Studies (MRID) Study
Classifications Are data
needed for
risk

assessment ? Justification and Assumptions EPA will Make
in Absence of Data

850.3030 Honey Bee toxicity of
residues on foliage No data available No Data are not require at this
time because it is not known whether the triggers are met for requiring this study per 40CFR Part 158 ( i.e. adult contact toxicity LD 50 < 11 μg a.i/bee).

850.6200 Earthworm
Subchronic Toxicity No data available No

--

Non

guideline study Honey bee adult
chronic oral toxicity

No data available Yes

Studies are needed as part of the tiered pollinator risk assessment approach. Non

guideline study Honey bee
larvae acute oral toxicity

Non

guideline study Honey bee
larvae chronic oral toxicity Yes

Non

guideline study (Tier 2) Field trial of
residues in pollen and

nectar Yes

850.3040 (Tier 2 or 3) Field Testing
for Pollinators Yes

Non

guideline study Semi

- field study with the Honey bee No data available Yes

850.4100 Seedling Emergence 47645915 Acceptable No

--

850.4150 Vegetative Vigor 47645916 Acceptable No

--

Shaded and bolded cells indicate that additional data are recommended for the corresponding data requirement.



### Table 2 3

. Terrestrial Ecological Effects Data for ETU

OCSPP
Guideline Data Requirement Submitted Studies (MRID) Study
Classifications Are data needed for risk

assessment ?

850. 2100 Avian oral toxicity 48343001 Study in review N/A

48437501 Study in review N/A

850.2100 Avian dietary toxicity 48417801 Acceptable

--

### 51 OCSPP
Guideline Data Requirement Submitted Studies (MRID) Study
Classifications Are data needed for risk

assessment ?

48417802 Acceptable

--

850.2300 Avian reproduction 48417801 Acceptable

--

48417802 Acceptable

--



## Data Justification Tables for Non

- Codified Exposure and Effects Studies with
Bees

Study Title: Honey bee Larvae Acute Oral Toxicity Rationale for Requiring the Data Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. With eusocial bees, pesticide residues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to the hive where devel oping larvae and pupae may be exposed. Therefore, potential adverse effects to developing bees could result from exposure to pesticide residues. Available toxicity studies do not address possible effects on brood (larvae and pupae) survival/development . Because of the potential for pollen and nectar to be contaminated with pesticide residues, and subsequently brought back to the hive, it is important to determine the acute toxicity of this compound to bee brood.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for bees using

the honey bee as a surrogate test species. The guidances discusses Tier I laboratory

- based acute toxicity

studies of individual honey bee larvae as a critical component of the screening

- level risk assessment process for examining potential risks from specific routes of exposure. The guidance be found at: http://www2.epa.gov/pollinator

- protection /pollinator

- risk

- assessment

- guidance . Additional guidance on

larval honey bee toxicity test design can be found in OECD Test Guideline 237 ( http://www.oecd

ilibrary.org/docserver/download/9713171e.pdf?expires=1422485600&id=id&accname=guest& checksum

=D8E07C2B1DF77BF096C3B29F55BF86A7 ). In some cases, information pertaining to acute toxicity to honey bee larvae may be obtained with the chronic honey bee larval test thereby negating the need for separate acute and chronic larval toxicity tests. Practical Utility of the Data

### 52 How will the data be used?

The Tier 1 acute toxicity d ata on honey bee larvae serve as a foundation for the screening

- level assessment of potential risk to non

- target organisms including federally listed threatened or endangered and non

- listed
terrestrial invertebrates , including pollinators, and/or modify their designated critical habitat from acute exposures to pesticides. The data will be used to reduce uncertainties associated with t he risk assessment for terrestrial invertebrates and will improve EPA’s understanding of the potential effects on terrestrial species and whether there is a differential sensitivity of larval bees relative to adult bees. If acute effects
data for larvae a re not available, risks to terrestrial insects from acute exposure will be assumed

.

How could the data impact the Agency’s future decision

- making? The data will inform the determination required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to non

- target species or is likely to adversely affect listed threatened or endangered species and/or modify their designated critical habitat. Without these data, EPA may need to presume risk which will limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could result in use restrictions.

Study Title: Honey Bee Adult Chronic Oral Toxicity Rationale for Requiring the Data

Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. With eusocial bees, p esticide residues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to the hive. Therefore, potential chronic effects t o adult honey bees and other pollinators from oral exposure to some pesticides could exist. Currently available toxicity studies do not address possible lethal and sublethal effects of chronic oral exposure on adult terrestrial invertebrates and
will assi st in determining whether the sensitivity of adult bees differs from that of earlier life stages. Because of the potential for pollen and nectar to be contaminated with pesticide residues, and subsequently brought back to the hive, it is important to dete rmine the chronic oral toxicity of this compound to adult honey bee s and other pollinators.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for bees using

the honey bee as a surrogate test species. The guidance s discusses Tier I laboratory

- based chronic oral toxicity studies of individual adult honey bee s as a critical component of the screening

- level risk assessment process for examining potential risks from specific routes of exposure. The guidance can be fo und at: http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guidance . Although study design

elements for the chronic 10

- day oral toxicity test w ith honey bees are similar to the OECD TG 213 acute oral toxicity test ( http://www.oecd

ilibrary.org/docserver/download/9721301e.pdf?expires=1422484908&id=id&accname=guest&checksum

=C38495D2A570AC2216CFB1F223D24AA7 ), EPA requires that the proposed protocol for this study be submitted for review and approval by EPA prior to init iating the test

. Practical Utility of the Data

How will the data be used?

The Tier 1 chronic toxicity d ata on adult bees serve as a foundation for the screening

- level assessment of potential risk to non

- target organisms including federally listed threatened or endangered species and non

listed terrestrial invertebrates , including pollinators, from chronic o ral exposures to pesticides. The data
will be used to reduce uncertainties associated with the risk assessment for terrestrial invertebrates and will improve EPA’s understanding of the potential direct and indirect lethal and sublethal effects on a broad range of terrestrial species, particularly insect pollinators and to determine whether adult toxicity differs substantially from other life stages evaluated in other Tier 1 tests. If chronic oral effects data for adults are not available, risks to terrest rial insects from chronic exposure will be assumed.

### 53 How could the data impact the Agency’s future decision

- making? The data will inform the determination required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to resu lt in unreasonable adverse effects to non

- target species or is likely to adversely affect listed threatened or endangered species and/or their designated critical habitat. Without these data, EPA may need to presume risk which will limit the flexibility o f pesticide products to comply with FIFRA and the ESA, and could result in use restrictions. Study Title: Honey Bee Larvae Chronic Oral Toxi city Rationale for Requiring the Data Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. For eusocial bees, pesticide residues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to the hive where larvae and pupae may be exposed. Therefore, potential effects to developing bees could result from chronic exposure to pesticide residues. Available toxicity studies do not address possible chronic effects on brood (larvae and pupae) survival. Because of th e potential for pollen and nectar to be contaminated with pesticide residues, and subsequently brought back to the hive, it is important to determine chronic larval/pupal toxicity and whether adult emergence is adversely affected. This study will provide i nformation on whether honey bee larvae differ in sensitivity from adult bees following chronic exposure.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for bees using

the honey bee as a surrogate test species. The guidances discusses Tier I laboratory

- based chronic toxicity

studies of individual honey bee larvae as a critical component of the screening

- level risk assessment process for examining potential risks from specific routes of exposure. The guidance can be found at: http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guidance

. Additional information

on larval honey bee toxicity repeat exposure test design can be found in the OECD draft guidance ( http://www.oecd.org/env/ehs/testing/Draft_GD_honeybees_rep_exp_for _2nd_CR_25_November_2013.p

df

). Although study design elements for the chronic 21

- day toxicity test with honey bee larvae have been drafted, EPA requires that the proposed protocol for this study be submitted for review and approval by EPA prior to initiat ing the test. Practical Utility of the Data

How will the data be used? The Tier 1 chronic toxicity d ata on bee larvae serve as a foundation for the screening

- level assessment of potential risk to non

- target organisms including federally listed threatened or endangered and non

- listed terrestrial invertebrates, including insect pollinators, from chronic exposures to pesticides. These data will
be used to reduce uncertainties associated with the risk assessment for terrestrial invertebrates and will improve EPA’s understanding of the potential direct and indirect lethal and sublethal effects on a broad range of terrestrial species, particularly insect pollinators. These data will also assist in determining whether early life stages of the be e differ in their sensitivity to pesticides relative to adults. If chronic effects data for larvae are not available, risks to terrestrial insects from chronic exposure will be assumed.

How could the data impact the Agency’s future decision

- making? The data will inform the determination required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to non

- target species or is likely to adversely affect listed threatened or endan gered species and/or modify their designated critical habitat. Without these data, EPA may need to presume risk which will limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could result in use restrictions.

### 54 Study Title: Semi

- field Testing for P ollinators (tunnel or colony feeding studies)
Rationale for Requiring the Data Tier II studies are conditional on the outcome of the screening

- level assessment where acute and/or chronic risk levels of concern have been exceeded for terrestrial invertebrates. Terrestrial invertebrates are likely to be impacted if exposed to pesticid es in various use settings. For eusocial bees, pesticide residues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to the hive and may adversely affect developing brood (egg, larvae, and pupae) and adult bees. Sc reening

- level (Tier 1 ) studies of individual bees do not address possible effects and/or exposure to pesticide residues at the colony

- level. Because of the potential for pollen and nectar to be contaminated with pesticide residues, and subsequently brough t back to the hive, it is important to determine whether bee colonies may be negatively affected under relatively controlled exposure conditions of a semi

- field study. In addition to providing effects data, these studies can provide data on pesticide resid ues in pollen/nectar of treated plants.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for bees using the honey bee as a surrogate test species. This guidance describes the tiered testing process and can be found

at: http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guidance

, Additional info rmation

on honey bee colony studies under semi

- field conditions can be found in the OECD Guidance 75
( http://www.oecd.org/officialdo cuments/publicdisplaydocumentpdf/?cote=env/jm/mono% 282007%2922&
doclanguage=en ). Due to the complexities of this study, EPA requires that the proposed protocol for this study be submitted for review EPA prior to initiating the test. Practical Utility of the Data

How will the data be used? Tier II colony

- level data will be used to assess potential risk to non

- target organisms including listed and

non

- listed terrestrial social invertebrate species and to determine whether effects observed in the screening

level (Tier I) laboratory

- based studi es of individual bees are evident in colony

- level studies under semi

- field

conditions. The Tier II semi

- field test of whole colonies is a relatively controlled study, i.e ., bees are confined to a specific area, that is designed to represent potential fiel d

- level exposure and account for hive dynamics, which are not achievable from other pollinator studies. This study will be used to determine whether adverse effects to insect pollinators at the whole colony level, may result for the use of pesticides and will help to refine risk estimates derived in the screening

- level risk assessment for beneficial terrestrial invertebrates. Measured residues in pollen/nectar can also be used to refine risk estimates derived from model

- based or

default values in the scre ening

- level assessment.

How could the data impact the Agency’s future decision

- making? The data will inform the determination required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to non

- target species or is likely to adversely affect federally listed threatened or endangered species or their designated critical habitat. Without these data, EPA may need to presume risk which will limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could result in significant use restrictions.

### 55 Study Title: Semi

- field Testing for P ollinators (tunnel or colony feeding studies) Rationale for Requiring the Data For eusocial bees, pesticide residues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to the hive and may adversely affect developing brood (egg, larvae, and pupae) and adult bees. Tier II feeding studies are conditional on the outcome of the screening

- level assessment where
acute and/or chronic risk levels of concern have been exceeded for terrestrial invertebrates based on Tier I studies of individual bees. Feeding studies utilize free foraging bee colonies that are “dosed” with specific quantities of test material and represent a means of ensuring exposure to the test material through spiked pollen and/or sugar solutions fed to the colony while still allowing the bees to forage freely. Since bee colonies are not confined to enclosures, colonies can be expo sed for longer duration periods without subjecting the bees to stress that typically results from Tier II tunnel studies. Available toxicity studies of individual bees (Tier 1) conducted to support screening

- level assessments do not address possible effec ts and/or exposure to pesticide residues at the colony

- level. It is therefore important to determine whether bee colonies may be negatively affected where bees are free foraging and have the option to collect/consume alternative forage items beyond the sp iked food. Since multiple dose levels can be more readily tested, feeding studies can help to define dose

- response relationships at the whole colony level.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for be es using the honey bee as a surrogate. This guidance describes the tiered testing process and can be found at: http://www2.epa.gov/pollinator

- protection/pollinat or

- risk

- assessment

- guidance

. Additional information on honey bee colony feeding studies can be found in the EPPO Guidance 170 ( www.nationalbeeunit.com/downloadDocument.cfm?id=191 )

. Although study design elements for the feeding study are available through the EPPO Guidance 170, EPA requires that the proposed protocol for this study be submitted for review and approval by EPA prior to initiating the test. Practical Utility of the Data

How will the data be used? Tier II colony feeding data will be used to assess potential risk to non

- target organisms including listed and

non

- listed terrestrial social invertebrate species. The colony feeding study is designed to represent potential
field

- level exposure and account for hive dynamics using longer duration exposure periods than are possible
in Tier II tunnel studies. This study will be used to determine whether potential adverse effects to insect pol linators at the whole colony level when bees are able to forage naturally beyond the spiked food. Results from the feeding study will help to refine the screening

- level risk assessment for beneficial terrestrial
invertebrates that were based on Tier I stu dies on individual bees. Since feeding studies can help to define a
dose

- response relationship at the colony level, the studies can provide a means of determining exposure thresholds below which the likelihood of adverse effects on colonies may be low.

H ow could the data impact the Agency’s future decision

- making?

The Tier II colony

- level data will be used to refine screening

- level risk estimates derived using Tier I laboratory

- based data on individual bees. The Tier II data will help to inform the deter mination required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable
adverse effects to non

- target species or is likely to adversely affect federally listed threatened or endangered species or the ir designated critical habitat. Without these data, EPA may need to presume risk which will limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could result in significant
use restrictions.

### 56 Study Title: Residues in Pollen and Nectar Rationale for Requiring the Data Terrestrial invertebrates are likely to be impacted if exposed to pesticides residues in various use settings. Pesticide residues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to hive all life stages may be exposed. For some pesticides, the quantification of pollinator

- relevant residues in treated flowering plants is needed, since pollinators will be exposed to residues from either current or prior season applicati ons (due to the potential for residues to accumulate in plants and trees). Residues in edible/transportable

- to

- hive parts of treated trees and plants, including (where appropriate), but not limited to, guttation water, sap/resins, whole plant tissue ( e.g. , leaves, stems), as well as blooming, pollen

- shedding, and nectar producing parts ( i.e. , flowers and, if present, extra

- floral nectaries) of plants may inform the potential for risk. Studies should be designed to provide residue data for crops and applic ation methods of

concern.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for bees using the honey bee as a surrogate. This can be found at: http://www2.epa.gov/pollinator

- protection/pollinator

risk

- assessment

- guidance

. Since residue studies are intended to provide exposure data in multiple matrices

and under specific application conditions, EPA requires that the protocol is submitted for review and approval by EPA prior to initiation of the study. Practical Utility of the Data

How will the data be used?

Measured residue d ata will be used to refine cons ervative estimates of pesticide exposure and reduce uncertainties associated with the Tier I exposure assessment by providing direct measurements of pesticide concentrations resulting from actual use settings. Measured residues may provide a more realistic understanding of exposure through contact or ingestion with which to calculate risk quotients for individual bees as well as to characterize exposure to the colony. If measured residue data are not available, risk
estimates for terrestrial insects will b e based on model generated or default values used to support the screening

- level assessment.

How could the data impact the Agency’s future decision

- making? The data will inform the determination required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to non

- target species or is likely to adversely affect federally listed threatene d or endangered species or their designated critical habitat. Without these data, EPA will have to rely on conservative estimates of exposure which may limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could result in use r estrictions.

### 57 

# 12 References

Food and Agriculture Organization of the United Nations. 2000. FAO PESTICIDE DISPOSAL
SERIES 8. Assessing Soil Contamination: A Reference Manual. Appendix 2. Parameters of pesticides that influence processes in t he soil. Editorial Group, FAO Information Division: Rome, 2000. http://www.fao.org/DOCREP/003/X2570E/X2570E00.htm

.

USEPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs . United States Environmental Protection Agency (USEPA). Environmental Fate and Effects Division. Office of Pesticide Programs. Available at http://www.epa.gov/espp/consultation/ecorisk

- overview.pdf (accessed 02/19/2014).

USEPA. 2006. Standard Soil Mobility Classification Guidance. Memorandum from Donald Brady dated April 21, 2006.

USEPA. 2010. Guidance for Reporting on the Environmental Fate and Transport of the Stressors of Concern in Problem Formulations for Registration Review, Registration Review Risk Assessments, Listed Species Litigation Assessments, New Chemical Risk Assessments, and Other Relevant Risk Assessments. Memorandum from Donald Brady dated January 25, 2010 ( http://www.epa.gov/pesticides/science/efed/policy_guidance/team _authors/endangered _species_reregistration_workgroup/esa_reporting_fate.htm

### 58 

# Appendix A

. Metiram Fate and Ecological Effects Bibliography

014601 Metiram Fate Chemistry Bibliography MRID

- Doc Number
Revised 27 June 2014

Product Chemistry Data

157997 BASF Wyandotte Chemical Corp. (1985?) Product Chemistry [Data]: Metiram. Unpublished compilation. 73 p.

40507102 Ohnsorge (1988) Amendment on Product Chemistry Submission Based on Discission ?sic| with EPA on September 11, 1987: Reg. Document No. 88/5007. Unpublished study prepared by BASF Aktiengesell

- schaft. 11 p.

41340002 Ackerman, J. (1989) Product Chemistry: ?Inert Chemical|: Lab Pro ject No.: SCC

- 3. Unpublished study prepared by Sherex Chemi

- cal Co. 15 p.

42461001 Ohnsorge, U. (1992) Product Chemistry: Product Identity and Composition, Beginning Materials and Manufacturing Process, and Discussion of the Formation Impurities of Poly ram DF (BAS 22 28 F): Lab Project Number: 3475: 92/10663. Unpublished study prepared by BASF Aktiengesellschaft. 86 p.

43064002 Ohnsorge, U. (1993) Identity of "Metiram Complex AI" in Polyram DF: Lab Project Number: 93/11278. Unpublished study prepared b y BASF Aktiengesellschaft. 38 p.

42461002 Tobia, A. (1992) Product Chemistry: Analysis and Certification of Product Ingredients, and Validation of Analytical Methods for Polyram DF (BAS 222 28 F): Lab Project Number: 3460: 3467: 4502. Unpublished study prepared by BASF Aktiengesellschaft. 91 p.



### 63

- 8 Solubility

MRID Citation Reference

147429 Keller, W.; Pawliczek, J. (1985) Solubility of Technical Metiram in Water: Report No. 2166. Unpublished study prepared by BASF. 7 p.

155159 Keller, W.; Pawliczek, J. (1985) [Physical and Chemical Character

- istics]. Unpublished compilation prepared by BASF AG. 9 p.

157997 BASF Wyandotte Chemical Corp. (1985?) Product Chemistry [Data]: Metiram. Unpublished compilation. 73 p.

40507101 Schnei der, A.; Redeker, J. (1988) Solubility of Metiram in Ethanol and DMSO: Reg. Document No. BASF 88/5006. Unpublished study prepared by BASF Aktiengesellschaft. 7 p.



### 63

- 11 Oct/Water partition Coef.

MRID Citation Reference

155159 Keller, W.; Pawliczek, J. (1985) [Physical and Chemical Character

- istics]. Unpublished compilation prepared by BASF AG. 9 p.

### 59 157997 BASF Wyandotte Chemical Corp. (1985?) Product Chemistry [Data]: Metiram. Unpublished compilation. 73 p.



### 161

- 1 Hydrolysis

MRID Citation Reference

001467

- 64 BASF AG (1981) Hydrolytical Stability: [Metiram]. Unpublished study. 4 p.

001551

- 89 Klein, W. (1985) Report on: Hydrolysis of the EBDC Fungicide Metiram". Unpublished study prepared by Fraunhofer Institut fur Umweltchemie und Oekotoxikologie. 97 p.

001619

- 37 Regenstein (1986) Hydrolysis of the EBDC Fungicide Metiram

- Com

- plex: [ Addend um ]. Unpublished study prepared by BASF Aktienge

- sellschaft. 4 p.

40576401 O'Grodnick, J.; Asshauer, J. (1988) HOE 070542

-- Substance Technical Abiotic Hydrolysis as a Function of pH. Unpublished Reviews prepared by Hoechst AG and Hoechst Celanese Corp. 4 p.

40466103 Carpenter, M. (1987) Hydrolysis as a Function of pH at 25°C of 14C

- Ethylenethiourea. Unpublished Study Prepa red by ABC Laboratories for Roam and Haas and Received Jan 18,1988 in Response to the Mancozeb Registration Standard. Acc. MRID
40466103.



### 161

- 2 Photodegradation

- water

MRID Citation Reference

001551

- 90 Klein, W. (1985) Report on: Water Photolysis of the EBDC Fungicide Metiram". Unpublished study prepared by Fraunhofer Institut fur Umweltchemie und Oekotoxikologie. 97 p.

001619

- 38 Regenstein (1986) Water Photolysis of the EBDC Fungicide Metiram

- Comple x: [ Addendum ]. Unpublished study prepared by BASF Aktien

- gesellschaft. 5 p.

40576402 O'Grodnick, J.; Asshauer, J. (1988) HOE 070542

- ?Carbon 14|

-- Photo

- degradation Studies in Water and Amendment to Report and Identi

- fication of Products
Formed after Aqueous Photolysis. Unpu

- blished study prepared by Hoechst AG and Hoechst Celanese Corp. 54 p.

40466101 Carpenter, M. (1987) Determination of the Photolysis Rate of 14C

- Ethylenethiourea on the Surface of Soil. Unpublished Study Prepared by ABC Laborator ies for Roam and Haas and Received Jan 18, 1988 in Response to the Mancozeb Registration Standard. Acc. 40466101



### 161

- 3 Photodegradation

- soil

MRID Citation Reference

001570

- 31 Klein, W. (1986) Report on Soil Photolysis of the EBDC Fungicide Metiram

complex. Unpublished study prepared by Fraunhofer Institut fuer Umweltchemie und Oekotoxikologie. 93 p.

### 60 40576403 O’Grodnick, J.; Asshauer, J. (1988) HOE 070542

— Photodegradation Stud ies on Soil: Supplement to. Unpublished study prepared by Hoechst AG and Hoechst Celanese Corp. 7 p.



### Aerobic soil metabolism

MRID Citation Reference

001552

- 88 Keller, E.; Huber, R. (1985) [The Fate of Metiram in Soil]: Rep. No. 2208. Unpublished compilation prepared by BASF AG. 29 p.

40576404 O’Grodnick, J.; Asshauer, J. (1988) HOE 070542

- ?Carbon 14|

-- Aerobic Soil
Metabolism and Amendment to Report: Supplemental to. Un

- published study prepared by Hoechst AG and Hoechst Celanese Corp. 6 p.

451452

- 03 Wright, M. (2000) Aerobic Soil Metabolism of (carbon

- 14) Metiram in Soil: Lab Project Number: XBL99042: RPT00597. Unpublished study prepared by
XenoBio tic Laboratories, Inc. 171 p.

459069

- 01 Staudenmaier, H. (2002) Aerobic Metabolism of BAS 222 F (Metiram) in Cashmere Soil: Final Report: Lab Project Number: 121479: 2002/1011913. Unpublished study prepared by BASF Aktiengesellschaft. 61 p.



### Anaerobic soil metabolism

MRID Citation Reference

001552

- 88 Keller, E.; Huber, R. (1985) [The Fate of Metiram in Soil]: Rep. No. 2208. Unpublished compilation prepared by BASF AG. 29 p.



### Aerobic aquatic metabolism

MRID Citation Reference

459334

- 01 Ebert, D. (2003) Degradation of BAS 222 F (Metiram) in Water/Sedi

- ment

- Systems Under Aerobic Conditions: Final Report: Lab Project Number: 115885: 2003/1001011. Unpublished study prepared by BASF Aktiengesellschaft. 93 p.



### 163

- 1 Leach/adsorption/desorption

MRID Citation Reference

146766 Biologische Bundesanstalt fur Land

- und Forstwirtschaft (1974) Leaching Behaviour of Pesticides. Unpublished study. 2 p.

405763

- 01 Spare, W. (1988) Leaching Characteristics of Parent Metiram: Pro

- ject No. 2501. Unpublished study prepared by Agrisearch Inc. 118 p.

### 61 40576405 O’Grodnick, J.; Asshauer, J. (1988) Adsorption/Desorption in the System Soil/Water and Addendum to Report : Supp lement to. Unpu

- 61 lushed study prepared by Hoechst AG and Hoechst Celanese Corp. 5 p.



### Terrestrial field dissipation

MRID Citation Reference

1722 Ranney, D. (1964) ?Field Studies with Terrazole (OM

- 2424) on Cotton|. (Unpublished study received Dec 16, 1964 under 1258

- 740; prepared by U.S. Delta States Agricultural Research Center, Delta Experiment Station, submitted by Olin Mathieson Chemical Corp., New York, N.Y.; CDL:005764

- F)

161935 Novak, R. (1986) Polyram Soil Dissipation: Determination of Polyram and Ethylenethiourea Residues: NPC Project No. 86

- 2001. Unpublished study prepared by NPC, Inc. in cooperation with Enviro

- Bio

- Tech, Ltd. 22 p.

414408

- 01 Bookbinder, M. (1990) Metiram a nd Ethylenethiorea: Dissipation in Soil After Application to Sugar Beets in California by Ground Equipment: Lab Project
Number: 42

- MET/90014. Unpublished study prepared by Orius Associates Inc., in cooperation with Morse Laboratories, Inc., and others. 200 p.

414408

- 02 Bookbinder, M. (1990) Metiram and Ethylenethiourea: Dissipation in Soil After Application to Sugar Beets in New York by Ground Equipment, 1988

- 1989: Lab Project Number: 42

- MET/90029. Unpub

- lished study prepared by Orius Associates Inc., in cooperation with Morse Laboratories, Inc., and others. 132 p.



### 165

- 1 Confined rotational crop

MRID Citation Reference

41904801 Merricks, L.; Lantz, L. (1991) Carbon 14

- Metiram Confined Rotation

al Crop Study: Lab Project Number: 2503. Unpublished study pre

pared by Agrisearch Inc. 73 p.

48122001 Bross, M.; Glaessgen, W.; Lutz, T. (2010) Confined Rotational Crop Study with (Carbon 14)

- BAS 222 F. Project Number: 243862, 2009/1017248. Unpublished study prepared by BASF Aktiengesellschaft. 418 p.



### Non

- Guideline Study

MRID Citation Reference

00146765 Kuhr, R.; Davis, A.; Bourke, J. (1974) Dissipation of guthion, se

vin, polyram, phygon and systox from apple orchard soil. Bulle

tin of Environmental Contamination & Toxicology 11(3)224

- 230.

00155162 Keller, E.; Huber, R. (1985) Summary of Metiram Soil Metabolism Studies. Unpublished study. 8 p.

### 62 40540007 Novak, R. (1988) Metiram and Ethylenethiourea: Summary of Storage Stability in Frozen Raw Agricultural Commodities and Processed Commodities: Project ID METIRAM

- 88

- 1001. Unpublished study. 17 p.

4054008 Novak, R. (1988) Metiram and Ethylenethiourea: Summary of Storage Stability in Frozen Raw Agricultural Commodities and Processed Commodities: Project ID METIRAM

- 88

- 1001. Unpublished study. 17 p.

40731001 Larese, J. (1988) Storage Stability of Metiram and Ethylenethiourea in Frozen Apple Processed Commodities: Laboratory Project ID: FMC

- 25

- 87 and

- 30

- 87. Unpublished study prepared by Enviro

- Bio

- Tech, Ltd. 88 p.

40731002 Larese, J. (1988) Storage Stability of Metiram and Ethylenethiourea in Frozen Potato Processed Commodities: Metiram and Ethylene

- thiourea Stability in Wet and Dry Potato Peel: Laboratory Pro

- ject ID: FMC

- 26

- 87,

- 31

- 87. Unpublished study prepared by Envir o

- Bio

- Tech, Ltd. 76 p.

40910401 U.S. Environmental Protection Agency (1988) GS644: Metiram: Regis

- tration Standard: Administrative Record. Unpublished compila

- tion ?with confidential attachment|. 1786 p.

43064001 Novak, R. (1993) Metiram Metaboli sm in Plants and Animals: Comparability to Metabolism of Other Ethylenebisdithiocarbamate Fungicides: Lab Project Number: 93/5160. Unpublished study prepared by NPC, Inc. 11 p.

44027901 US EPA (1996) Administrative Record for the Special Review of EBDC's. Unpublished Compilation (with Confidential Attachment). 5583 p.

46145401 Bedosky, S. (2003) EBDC/ETU Task Force National Drinking Water Monitoring Survey:Final Report. Project Number: ETU/2000/01, ETU/0301, 004/06942/04. Unpublished study prepared by Levine

- Fricke, Inc., Enviro

- Test Laboratories (ETL), and Morse Laboratories. 572 p.

46547701 Bross, M. (2005) Metiram (BAS 222 F): Summary of Residue Data in Grapes Including Ana lytical Methods and Process Fraction Studies Supporting an US Import Tolerance Petition for Wine: Final Report. Project Number: 2005/1007595, 2002/100493, 2003/1001361. Unpublished study prepared by BASF Aktiengesellschaft. 40 p.



### ETU Studies : MRID No. (D ER file reference)

Hydrolysis

404661

- 03 Carpenter, M. (1987) Hydrolysis as a Function of pH AT 25? Degrees C OF ?Carbon 14|

- Ethylenethiourea: ABC Final Report No. 36287. Unpublished study prepared by Analytical Bio

- Chemistry Labs., Inc. 543 p.

Photolysis in Water

### 63 404661

- 02 (2082324) Carpenter, M.; Fennessey, M. (1987) Determination of the Photolysis Rate of ?Carbon 14|

- Ethylenethiourea in pH 7 Aqueous Solution: ABC Re

- amended Final Report No. 36288. Unpublished study pre

- pared by Analytical Bi o

- Chemistry Labs., Inc. 658 p.

Photolysis on Soil

404661

- 01 (2082324) Carpenter, M. (1987) Determination of the Photolysis Rate of Ethylenethiourea (ETU) on the Surface of Soil: ABC Final Report No. 36289. Unpublished study prepared by Analytical Bio

- Che mistry Labs., Inc. 504 p.

Aerobic Soil Metabolism

452251

- 01 Wright, M. (2000) Aerobic Soil Metabolism Degradation Rate Determination for Ethylenethiourea (ETU) on Soil: Lab Project Number: XBL 99045: RPT00643: AR98197. Unpublished study prepared by Xenobiotic Labs., Inc. 160 p.

4515 464

- 01 Wright, M. (2000) Aerobic Soil Metabolism Degradation for Ethylemethiourea (ETU) on Soil: Report of Degradation Rate Determination for ETU on New York Silt Loam Soil at 70% and 40% Normal Moisture Holding Capacity and 25 (degrees) C: Lab Project Number: XBL 99045: RPT00598: KP

- 98

- 39. Unpublished study prepared by XenoBiotic Laboratories. 123 p.01

- Jun

- 2000

Volatility

- Laboratory

42301501 Obrist, J. (1992) Laboratory Volatility Studies on ?carbon 14|

- ETU: Final Report: Lab Project Number:
HLA 6101

- 109. Unpublished study prepared by Hazleton Laboratories America, Inc. 24 p. 04

- May

- 1992

ECMs and ILVs

448804

- 01 Bruns, G.; Tauber, R.; Gottschalk, R. (1999) Validation of the Method of Analysis for Ethylenethiourea (ETU) in Water by LC/MS/MS: Lab Project Number: ETU01ETL: ETL99RH01.PRO: 99RHC42.REP. Unpublished study prepared by Enviro

- Test Laboratories. 146 p.

451514

- 01 Connolly, P. (2000) Independent Laboratory Analytical Method: Method for the Analysis of Ethylen ethiourea (ETU) in Water by LC/MS/MS (MS 178.00) Revision 2: Lab Project Number: 002

- 342: 00P

- 002

- 342: MS 178.00. Unpublished study prepared by Centre Analytical Laboratories, Inc. 88 p. {OPPTS 850.7100}

Monitoring Data

45570301 Bedosky, S. (2001) EBDC/ETU Task Force National Drinking Water Monitoring Survey: Lab Project
Number: ETU

- 2000

- 01: ETU

- 0101: 6942. Unpublished study prepared by LFR Levine Fricke. 394 p. 21

- Dec

- 2001

45708301

### 64 Bedosky, S. (2002) EBDC/ETU Task Force National Drinking Water Mon itoring Survey: Lab Project
Number: ETU

- 0201: 6942: ETU

- 2000

- 01. Unpublished study prepared by LFR Levine

- Fricke. 353 p. 28

- Jun

- 2002

45836401 Bedosky, S. (2002) EBDC/ETU Task Force National Drinking Water Monitoring Study: Interim Report: Lab Project Num ber: ETU

- 2000

- 01: ETU

- 0202: 6942. Unpublished study prepared by LFR Levine

- Fricke,
Enviro

- Test Laboratories, and Morse Laboratories 366 p. 13

- Jan

2003

46145401 Bedosky, S. (2003) EBDC/ETU Task Force National Drinking Water Monitoring Survey:Final Report. Project Number: ETU/2000/01, ETU/0301, 004/06942/04. Unpublished study prepared by Levine

- Fricke, Inc., Enviro

- Test Laboratories (ETL), and Morse Laboratories. 572 p.
05

- Dec

- 2003

46319901 Ollinger, J. (2004) EBDC/ETU Task Force Response to U.S. E PA's Draft Science Chapter for the Environmental Fate and Ecological Risk Assessment for Ethylenethiourea (ETU) Dated June 2, 2004. Project Number: EBDC/FQPA/2004/01. 38 p. 15

- Jul

- 2004

46480002 Ollinger, J. (2005) EBDC/ETU Task Force Response to U.S. EPA's Draft Science Chapter for the Environmental Fate and Ecological Risk Assessment for Ethylenethiourea (ETU) Dated October 20, 2004. Project Number: EBDC/FQPA/2005/01. Unpublished study prepared by EBDC/ETU Task Force. 24 p. 23

- Feb

- 2005



## 014601 Metira m Eco Effects Bibliography

71

- 1 Avian Single Dose Oral Toxicity

MRID Citation Reference

40656901 Fletcher, D. (1988) Metiram Technical: 21

- day Acute Oral LD50 Study in Bobwhite Quail: Laboratory Project ID: 87 QD 99. Unpublished study prepared by Bio

- Life Associates, Ltd. 25 p.

48343001 Hubbard, P.; Beavers, J. (2010) Ethylenethiourea: An Acute Oral Toxicity Study with the Northern Bobwhite. Project Number: 697/101, 2010/1. Unpublished study prepared by Wildlife International, Ltd. 57 p.



### 71

- 2 Avian Dietary Toxicity

MRID Citation Reference

88907 Piccirillo, V.J.; Davis, K.; Vilchek, L.; et al. (1980) Eight

- day Dietary LCI50^ Study in Bobwhite Quail with RH

- 8817: Project 202

- I. Final rept. (Unpublished study received Aug 6, 1981 under 707

- EX

- 98; prepared by Borriston Research

### 65 Laboratories, Inc., su bmitted by Rohm & Haas Co., Philadelphia, Pa.; CDL:
070257

- M)
RH

- 8817= ethyl acifluorfen (114403)

88908 Piccirillo, V.J.; Reynolds, R.; Vilcoke, L.; et al. (1980) Eight

- day Dietary LCI50^ Study in Mallard Ducks with RH

- 8817: Project #202

- H. Final rept. (Unpublished study received Aug 6, 1981 under 707

- EX

- 98; prepared by Borriston Research Laboratories, Inc., submitted by Rohm & Haas Co., Philadelphia, Pa.; C DL:
070257

- N)
RH

- 8817= ethyl acifluorfen (114403)

108004 Fink, R. (1974) Final Report: Eight

- day Dietary LCI50^

-- Bobwhite Quail: Project No.
104

- 105. (Unpublished study received Apr 2, 1974 under 279

- 2032; prepared by Truslow Farms, Inc., submitted by FM C Corp., Philadelphia, Pa.; CDL:132451

- A)

108005 Fink, R. (1974) Final Report: Eight

- day Dietary LCI50^

-- Mallard Ducks: Project No.
104

- 106. (Unpublished study received Apr 2, 1974 under 279

- 2032; prepared by Truslow Farms, Inc., submitted by FMC Corp., Philadelphia, Pa.; CDL:132451

- B)

48417801 Hubbard, P.; Beavers, J. (2011) Ethylenethiourea: A Dietary LC 50 Study with the Northern Bobwhite. Project Number: 697/103, 2010/3. Unpublished study prepared by Wildlife International, Ltd. 66 p.

48417802 Hubb ard, P.; Beavers, J. (2011) Ethylenethiourea: A Dietary LC50 Study with the Mallard. Project Number: 697/104, 2010/4. Unpublished study prepared by Wildlife International, Ltd. 65 p.



### 850.2300 71

- 4 Avian Reproduction

MRID Citation Reference

41082001 Fletcher, D.; Pedesen, C. (1989) Metiram Premix 95%: Toxicity and Reproduction Study in Bobwhite Quail: BLAL No. 87 QR 29. Unpub

- lished study prepared by
Bio

- Life Associates, Ltd. 90 p.

41156101 Munk, R. (1989) One Generation Reproduction Study with Metiram

- Premix 95% on the Mallard Duck (Anas platyrhynchos L.) by Admin

- istration in the Diet: Project No. 72W0116/88006: BASF Registra

- tion Document No. BASF: 89/0227. Unpublished study prepared by Basf Aktiengesellschaft. 124 p.

42539102 Munk, R. (1992) 1

- generation Reproduction Study with Metiram Premix on the Mallard Duck by Administration in the Diet: Lab Project Number: 72W0698/90059: 92/11151. Unpublished study prepared by BASF Aktiengesells chaft. 214 p.

48819701 Temple, D.; Martin, K.; Beavers, J. et al. (2012) Ethylenethiourea: A Reproduction Study with the Northern Bobwhite: Final Report. Project Number: 697/107, 2010/5. Unpublished study prepared by Wildlife International, Ltd. 195p.

4 8819702 Temple, D.; Martin, K.; Beavers, J. et al. (2012) Ethylenethiourea: A Reproduction Study with the Mallard: Final Report. Project Number: 697/108, 2010/6. Unpublished study prepared by Wildlife International, Ltd. 196p.



### 850.1075 72

- 1 Acute Toxicity to Freshwater Fish

### 66 MRID Citation Reference

88903 Kuc, W.J. (1977) The Acute Toxicity of RH

- 8817 Technical (75

- 85% Active Ingredient) Lot #WDW 47:9

- 1 to Bluegill Sunfish, ?~Lepomis macrochirus~Rafinesque: UCES Proj. 11506

- 33

- 07. (Un

- published study received Aug 6, 1981 under 707

- EX

- 98; prepared by Union Carbide Corp., submitted by Rohm & Haas Co., Phila

- delphia, Pa.; CDL:070257

- I)
RH

- 881 7= ethyl acifluorfen (114403)

88904 Kuc, W.J. (1977) Acute Toxicity of RH

- 8817 Technical (75

- 85% Active Ingredient)
Lot #WDW 47:9

- 1 to Rainbow Trout,~Salmo gairdneri~ Richardson : UCES Proj.
11506

- 33

- 07. (Unpublished study received Aug 6, 1981 under 707

- EX

- 98; prepared by Union Carbide Corp., submitted by Rohm & Haas Co., Philadelphia, Pa.; CDL:070257

- J)
RH

- 8817= ethyl acifluorfen (114403)

88905 Union Carbide Corporation (1977) The Acute Toxicity of RH

- 8817 Technical (75

- 85% Active Ingredient) Lot #WDW 47:9

- 1 to the Channel Catfish,~Ictalurus punctatus~Rafinesque: UCES Proj. # 11506

- 33

- 07. (Unpublished study received Aug 6, 1981 under 707

- EX

- 98; submitted by Rohm & Haas Co., Phil adelphia, Pa.; CDL:070257

- K)
RH

- 8817= ethyl acifluorfen (114403)

40497011 Munk, R. (1986) Report on the Study of the Acute Toxicity: Name of Test Substance: BAS 222 28 F/ Polyram Combi DF. Animal Species: Rainbow Trout (Salmo gaidneri Rich.): Laboratory Project ID 85/400 (12F400/85): Reg. Doc. #BASF 88/0475. Unpublished study prepared by BASF Aktiengesellschaft. 23 p.

40945501 Bowman, J. (1988) Acute Toxicity of ?Carbon 14|

- Metiram to Bluegill Sunfish (Lepomis macrochirus): ABC Lab. Proj. ID 36982. Unpu b

- lished study prepared by Analytical Bio

- Chemistry Laboratories, Inc. 123 p.

43525001 Monk, R. (1994) Acute Toxicity Study on the Rainbow Trout of BAS 222 28 F in a
Flow

- Through System for 96 Hours: Lab Project Numbers: 94/10920: PCP03089: 94/161. Unpu blished study prepared by BASF Aktiengesellschaft. 47 p.

44224401 Munk, R. (1996) BAS 222 28 F

-- Acute Toxicity Study on the Bluegill Sunfish (Lepomis macrochirus RAF.) in a Flow

- Through System (96 Hours): Lab Project Number: 14F0265/965056: 96/10978. Unp ublished study prepared by BASF Aktiengesellschaft. 46 p.

48151302 Minderhout, T.; Martin, K.; Krueger, H.; et al. (2010) Metiram: A 96

- Hour Flow Through Acute Toxicity Test with the Fathead Minnow. Project Number: 147A/257, 310511, 2010/7010878. Unpubli shed study prepared by Wildlife International, Ltd. 54 p.

45910401 see
600016

Also 46020903 

### Zok, R. (2001) Acute Toxicity Study on the Rainbow Trout (Oncorhynchus mykiss Walbaum 1792) in a Static System (96 Hours). Project Number: 12F0533/005042,

146099. Unpublished study prepared by BASF Aktiengesellschaft. 43 p



### .

85199 

### Schoenig, G. (1967) Report to Niagara Chemical Division, FMC Corporation:

Four

- day Fish Toxicity Study on Polyram 5 Dust: IBT No. A5208. (Unpublished study received Jul 10, 1967 under unk nown admin. no.; prepared by Industrial Bio

Test Labora

- tories, Inc., submitted by FMC Corp., Philadelphia, Pa.; CDL:
105214

- B)

### 67 97893 

### Schoenig, G. (1967) Report to Niagara Chemical Division, FMC Corporation:

Four

- day Fish Toxicity Study on Polyram 80 WP : IBT No. A5208. (Unpublished study received Jul 10, 1967 under unknown admin. no.; prepared by Industrial Bio

Test Laboratories, Inc., submitted by FMC Corp., Philadelphia, Pa.; CDL: 105214

- A)



### 850.1010 72

- 2 Acute Toxicity to Freshwater Inv ertebrates

MRID Citation Reference

88906 Vilkas, A.G.; Morrissey, A.E. (1979) The Acute Toxicity of RH

- 8817 Technical (80% Active Ingredient) to the Water Flea Daphnia magna Straus: UCES Project
No. 11506

- 33

- 31. (Unpublished study received Aug 6, 1981 under 707

- EX

- 98; prepared by Union Carbide Co rp., submitted by Rohm & Haas Co., Philadelphia, Pa.; CDL:070257

- L)
RH

- 8817= Mixture of metiram and ethyl acifluorfen (114403)

40497003 Mueller, ?. (1981) Metiram BAS 222

- F

-- Acute Toxicity to the Water

- flea Daphnia magna Straus: Laboratory Project ID 1/0020/X/81: Reg.Doc. #BASF 81/0339. Unpublished study prepared by BASF Aktiengesellschaft. 12 p.

43525002 Jatzek, ?. (1994) Determination of the Acute Toxicity of BAS 222 28 F to the Water Flea Daphnia magna Straus for 48 Hours: Lab Project Numbers: 94/10671: 94/0839/50/1: 94/082. Unpublished study prepared by BASF Aktiengesellschaft. 31

p.

44301101 Maisch (1997) Determination of the Acu te Effect of BAS 222 28 F (Metiram) on the Swimming Ability of the Water Flea, Daphnia magna Straus: Final Report: Lab Project Number: 97/10538: PCP04287: 96/0599/50/1. Unpublished study prepared by BASF Aktiengesellschaft. 27 p.

48151301 Minderhout, T.; Martin, K.; Krueger, H.; et al. (2010) Metiram: A 48

- Hour Flow

Through Acute Toxicity Test with the Cladoceran (Daphnia magna). Project Number: 147A/252, 310512, 2010/7010877. Unpublished study prepared by Wildlife International, Ltd. 54 p.

45910402 see PC
600016

Also 46020901 

### Hisgen, M. (2000) Reg No. 146099: Determination of the Acute Effect on the Swimming Ability of the Water Flea Daphnia Magna Straus: Final Report. Project Number: 00/0533/50/1. Unpublished study prepared by BASF Aktiengesellschaft. 25 p.



### 72

- 3 Acute Toxicity to Estuarine Marine Organisms

MRID Citation Reference

127865 Armstrong, D.; Buchanan, D.; Caldwell, R. (1976) A mycosis caused by lagenidium sp. in laboratory

- reared larvae of the dungeness crab, cancer magister, and possible chemical treatments. Jour

- nal of Invertebrate Pathology 28:329

- 336. (Also In unpublished s ubmission received Apr 21, 1983 under 677

- 313; submitted by Diamond Shamrock Agricultural Chemicals, Cleveland, OH; CDL: 071552

- D)

### 68 48151303 Minderhout, T.; Martin, K.; Krueger, H.; et al. (2010) Metiram: A 96

- Hour Flow Through Acute Toxicology Test with the Sheepshead Minnow (Cyprinodon variegatus). Project Number: 147A/258, 310513, 2010/7010879. Unpublished study prepared by Wildlife International, Ltd. 53 p.

48151304 Minderhout, T.; Martin, K.; Krueger, H.; et al. (2010) Metiram: A 96

- Hour Flow

Through Acute Toxicity Test with the Saltwater Mysid (Americamys bahia). Project Number: 147A/253A, 310515, 2010/7010900. Unpublished study prepared by Wildlife International, Ltd. 54 p.

48151305 Minderhout, T.; Martin, K.; Krueger, H.; et al. (2010) Metiram: A 96

- Hour Shell Deposition Test with the Eastern Oyster (Crassostrea virginica). Project Number: 147A/259, 310514, 2010/7010901. Unpublished study prepared by Wildlife International, Ltd. 55 p.



### 72

- 4 Fish Early Life Stage/Aquatic Invertebrate Life Cycle Study

MRID Citation Reference

43770401 Monk, R. (1990) Sublethal Toxic Effects of Polyram WG (BAS 222 28 F) on Rainbow Trout (Oncorhynchus mykiss Walbaum) in a Flow

- Through System for 28 Days: Lab Project Number: 90/10320: 90/10319: 42F0724/895238. Unpublished study prepared by BASF Aktiengesel lschaft. 88 p.

43770402 Fritsch, H. (1990) Determination of the Longtern Effects of Polyram WG BAS 222
28 F Prod.

- Nr. 81708 on the Parthenogenetic Reproduction Rate of Daphnia magna for 21 Days: Lab Project Number: 90/0310: 1891809: 3/1809/89

- 1891809.
Un published study prepared by BASF Aktiengesellschaft. 63 p.

44301102 Maisch (1997) Determination of the Chronic Effect of BAS 222 28 F (Metiram) on the Reproduction of the Water Flea, Daphnia magna Straus in a Flow

- Through Test System: Final Report: Lab Project Number: 97/10521: 96/0599/52/1: 97/10537. Unpublished study pre pared by BASF Aktiengesellschaft. 42 p. {OPPTS 850.1300}

45933402 Junker, M. (2002) Effect of Multiple Applications of BAS 222 28 F on the Rainbow Trout (Oncorhynchus mykiss) in a Chronic, Juvenile Growth Test: Final Report: Lab Project Number: 140305: 2 002/1005264. Unpublished study prepared by BASF Aktiengesellschaft. 55 p. {OPPTS 850.1400}

48392001 Minderhout, T; Martin, K.; Krueger, H.; et al. (2010) Metiram: A Flow

- Through Life

Cycle Toxicity Test with the Cladoceran (Daphnia magna). Project Number : 147A/275, 395432, 2010/7014945. Unpublished study prepared by Wildlife International, Ltd. 76 p.

48392002 Minderhout, T.; Martin, K.; Krueger, H.; et al. (2010) Metriram: A Flow

- Through
Life

- Cycle Toxicity Test with the Saltwater Mysid (Americamysis bah ia). Project Number: 147A/260, 375793, 2010/7015187. Unpublished study prepared by Wildlife International, Ltd. 145 p.

48246303 Minderhout, T.; Martin, K.; Krueger, H.; et al. (2010) Metiram: An Early Life

- Stage Toxicity Test with the Fathead Minnow (Pime phales promelas). Project Number: 147A/256, 310516, 2010/7012795. Unpublished study prepared by Wildlife International, Ltd. 92 p.



### 122

- 2 Aquatic plant growth

### 69 MRID Citation Reference

43199601 Dohmen, G. (1990) Effects of BAS 222 28 F on the Growth of the Green Alga Ankistrodesmus bibraianus: Lab Project Number: P90/E008: 90/0114: 2985. Unpublished study prepared by BASF Aktiengesellschaft. 27 p.

45910403 see PC
600016

46020902 

### Reuschenbach, D. (2000) Reg No. 146099: Determination of the Inhibitory Effect on the Cell Multiplication of Unicellular Green Algae: Final Report. Project Number: 00/0533/60/1. Unpublished study prepared by BASF Aktiengesellschaft. 27 p

46462904 

### Palmer, S.; Kendall, T .; Krueger, H. (2001) Ethylene Urea: A 96

- Hour Toxicity Test with the Freshwater Alga (Selenastrum capricornutum): Final Report. Project Number: 299A/116. Unpublished study prepared by Wildlife International, Ltd. 49

p.



### 850.4100 Terrestrial plant t oxicity, Tier 1 (seeding emergence)

MRID Citation Reference

47645915 Porch, J.; Krueger, H.; Martin, K.; et al. (2008) Polyram (BAS 222 28 F): A Toxicity Test to Determine the Effects of the Test Substance on Seedling Emergence of Ten Species of Plants. Project Number: 147/232, 310518, 2008/7015442. Unpublished study prepared by Wildlife International, Ltd. 107 p.



### 850.4150 Terrestrial plant toxicity, Tier 1 (vegetative vigor)

MRID Citation Reference

47645916 Porch, J.; Krueger, H.; Martin, K.; et al. (2008) Polyram (BAS 222 28 F): A Toxicity Test to Determine the Effects of the Test Substance on Vegetative Vigor of Ten Species of Plant. Project Number: 147/233, 310519, 2008/7019314. Unpublished study prepared by Wildlife Internationa l, Ltd. 138 p.



### 850.4225 Seedling emergence, Tier II

MRID Citation Reference

47645915

- repeated in
Tier I Porch, J.; Krueger, H.; Martin, K.; et al. (2008) Polyram (BAS 222 28 F): A Toxicity
Test to Determine the Effects of the Test Substance on Seedling Emergence of Ten Species of Plants. Project Number: 147/232, 310518, 2008/7015442. Unpublished study prepared by Wildlife International, Ltd. 107 p.



### 850.4250 Vegetative vigor, Tier II

MRID Citation Reference

### 70 47645916 Porch, J.; Krueger, H.; Martin, K.; et al. (2008) Polyram (BAS 222 28 F): A Toxicity Test to Determine the Effects of the Test Substance on Vegetative Vigor of Ten Species of Plant. Project Number: 147/233, 310519, 2008/7019314. Unpublished study prepared by Wildlife International, Ltd. 138 p.

48745701 Brausch, J. (2012) BASF Response to EPA Data Evaluation Record (DERs) for Metiram (BAS 222 F)

- Ecotoxicology. Project Number: 147/233, 2012/7000233. Unpublished study prepared by BASF Corporation. 18p.



### 850.5400 Algal toxicity, Tiers 1 and II

MRID Citation Reference

47645917 Minderhout, T.; Martin, K.; Krueger, H.; et al. (2008) Polyram (BAS 222 28 F): A
96

- Hour Toxicity Test with the Marine Diatoms (Skeletonema costatum). Project
Number: 147A/237, 345792, 2008/7018037. Unpublished study prepared by Wildlife International, Ltd. 57 p.

47645918 Minderhout, T.; Martin, K.; Krueger, H.; et al. (2008) Polyram (BAS 222 28 F): A
96

- Hour Toxicity Test with the Freshwater Diatom (Navicula pelliculo sa). Project Number: 147A/235, 345791, 2008/7015288. Unpublished study prepared by Wildlife International, Ltd. 56 p.

47645919 Minderhout, T.; Martin, K.; Krueger, H.; et al. (2008) Polyram (BAS 222 28 F): A
96

- Hour Toxicity Test with the Fresh Water Alga (Anabaena flos

- aquae). Project Number: 147A/234, 345790, 2008/7015287. Unpublished study prepared by Wildlife International, Ltd. 56 p.

47645920 Minderhout, T.; Martin, K.; Krueger, H.; et al. (2009) Polyram (BAS 222 28 F): A
96

- Hour Toxicity Test with t he Fresh Water Alga (Pseudokirchneriella subcapitata). Project Number: 147A/236, 345789, 2009/7000035. Unpublished study prepared by Wildlife International, Ltd. 57 p.

48745701 Brausch, J. (2012) BASF Response to EPA Data Evaluation Record (DERs) for Metiram (BAS 222 F)

- Ecotoxicology. Project Number: 147/233, 2012/7000233. Unpublished study prepared by BASF Corporation. 18p.

49079801 Dobbins, L.; Martin, K.; Porch, J. (2013) Polyram (BAS 222 28 F): A 96

- Hour Toxicity Test with the Marine Diatom (Ske letonema costatum). Project Number: 147P/103, 431843, 2013/7000406. Unpublished study prepared by Wildlife International, Ltd. 58p



### 141

- 1 Honeybee Acute Toxicity

MRID Citation Reference

### 71 00001999 Atkins, E.L., Jr. and L.D. Anderson (1967) Toxicity of Pesticides and Other Agricultural Chemicals to Honey Bees: Laboratory Studies. (Unpublished Study Received Jan. 30, 1969 under 9G0802; Prepared by Univ. of California

- Riverside, Dept. of Entomology, Submitted by Hercules, Inc., Agricultural Chemicals,
W ilmington, Del., CDL: 093111

- D)

66220 later
132710 Atkins, E.; Anderson, L.; Kellum, D.; et al. (1977) Protecting Honey Bees from Pesticides. Riverside, CA: Univ. of California. (Leaflet 2883; also In unpublished submission received Nov 2, 1983 under 239

- 2507; submitted by Chevron Chemical Co., Richmond, CA; CDL:251760

- B)

49403401 Schmitzer, S. (2005) Effects of BAS 222 28 F (Acute Contact and Oral) on Honey Bees (Apis mellifera L.) in the Laboratory. Project Number: 2005/1012879, 24/94/36, 25351035. Unpu blished study prepared by Institut fuer Biologische Analytik und Consulting IBACON. 31p



### 850.1735 Acute Toxicity Tests

- Sediment Invertebrates

MRID Citation Reference

48246301 Thomas, S.; Martin, K.; Krueger, H.; et al. (2010) Metiram: A 10

- Day Flow

- Through Survival and Growth Sediment Toxicity Test with Chironomus tentans Using Spiked Sediment. Project Number: 147A/261, 310522, 2010/7012893. Unpublished study prepared by Wildlife International, Ltd. 77 p.

48246302 Thomas, S.; Martin, K.; Krueger, H.; et al. (2010) Metiram: A 10

- Day Flow

- Through Whole Sediment Toxicity Test with Leptocheirus plumulosus Using Spiked Sediment. Project Number: 147A/262, 310523, 2010/7012894. Unpublished study prepared by Wildlife International, Ltd. 69 p.



### Non

- Guideline Study

MRID Citation Reference

45534701 Lamb, IV, J.; Hentz, K.; Matthews, S.; et al. (2001) Analysis of Common Mechanisms of Toxicity for Ethylenebisdithiocarbamates and Other Dithiocarbamates. Unpublished study prepared by BBL Sciences. 111 p.

45933401 Ebert, D. (2003) Degradation of BAS 222 F (Metiram) in Water/Sediment

- Systems under Aerobic Conditions. Unpublished Study Performed by BASF Agricultural Center Limburgerhof, Germany; Sponsored and Submitted by BASF Corporation, Agricultural Products, Research Triangle Park, NC. BASF Registratio n Document No: 2003/1001011. Experiment Initiated February 14, 2002 and Completed February 26, 2003 (p.15). Final Report Issued on March 24, 2003. 

## 600016 ETU Eco Effects Bibliography

850.2100 71

- 1 Avian acute oral toxicity test

MRID Citation Reference

### 72 48437501 Hubbard, P.; Beavers, J. (2011) Ethylenethiourea: An Acute Oral Toxicity Study with the Zebra Finch (Poephila guttata). Project Number: 697/102, 2010/2. Unpublished study prepared by Wildlife International Ltd. 60 p.

48343001 Hubbard, P.; Beavers, J. (2010) Ethylenethiourea: An Acute Oral Toxicity Study with the Northern Bobwhite. Project Number: 697/101, 2010/1. Unpublished study prepared by Wildlife International, Ltd. 57 p.



### 850.2200 71

- 2 Avian Dietary Toxicity

MRID Citation Referen ce

48417801 Hubbard, P.; Beavers, J. (2011) Ethylenethiourea: A Dietary LC 50 Study with the Northern Bobwhite. Project Number: 697/103, 2010/3. Unpublished study prepared by Wildlife International, Ltd. 66 p.

48417802 Hubbard, P.; Beavers, J. (2011) Ethylenethiourea: A Dietary LC50 Study with the Mallard. Project Number: 697/104, 2010/4. Unpublished study prepared by Wildlife International, Ltd. 65 p.



### 850.2300 71

- 4 Avian Reproduction

MRID Citation Reference

48819701 Temple, D.; Martin, K.; Beavers, J. et al. (2012) Ethylenethiourea: A Reproduction Study with the Northern Bobwhite: Final Report. Project Number: 697/107, 2010/5. Unpublished study prepared by Wildlife International, Ltd. 195p.

48819702 Temple, D.; Martin, K.; Beavers, J. et al. (2012) Ethylenethiourea: A Reproduction Study with the Mallard: Final Report. Project Number: 697/108, 2010/6. Unpublished study prepared by Wildlife International, Ltd. 196p.



### 72

- 1 Acute Toxicity to Freshwater Fish

MRID Citation Reference

45910401 Zok, S. (2001) Acute Toxicity Study on the Rainbow Trout (Oncorhynchus mykiss Walbaum 1792) in a Static System (96 Hours): Ethylenethiourea (ETU): Lab Project Number: 12F0533/005042 : 2001/1001877: PCP06082. Unpublished study prepared by BASF Aktie ngesellschaft. 44 p.

46020903 Zok, R. (2001) Acute Toxicity Study on the Rainbow Trout (Oncorhynchus mykiss Walbaum 1792) in a Static System (96 Hours). Project Number: 12F0533/005042

, 146099. Unpublished study prepared by BASF Aktiengesellschaft. 43 p.



### 850.1075 Fish acute toxicity test, freshwater and marine

MRID Citation Reference

### 73 46462902 Palmer, S.; Kendall, T.; Krueger, H. (2001) Ethylene Urea: A 96

- Hour Static Toxicity Test with the Rainbow Trout (Oncorhynchus mykiss): Final Report. Project Number: 299A/115. Unpublished study prepared by Wildlife International, Ltd. 37 p.

47441201 Soucy, K. (2008) Ethylenethiourea

- Acute Toxicity to Sheepshead Minnow (Cyprinodon variegatus) Under Static Conditions, Following OPPTS Draft Guideline
850.1075. Project Number: 13921/6105, 2007/04. Unpublished study prepared by Springborn Smithers Laboratories. 55 p.

47441202 Soucy, K. (2008) Ethylenethiourea

- Acute Toxicity to Bluegill Sunfish (Lepomis macrochirus) Under Static Conditions, Following OPPTS Draft Guideline 850.1075. Project Number: 13921/6104, 2007/05. Unpublished study prepared by Springborn Smithers Laboratories. 55 p.

45910401
46020903 Zok, S. (2001) Acute Toxicity Study on the Rainbow Trout (Oncorhynchus mykiss Walbaum 1792) in a Static System (96 Hours): Ethylenethiourea (ETU): Lab Project Number: 12F0533/005042: 2001/1001877: PCP06082. Unpublished study prepared by BASF Aktiengesellschaft. 44 p.



### 72

- 2 Acute Toxicity to Freshwater Invertebrates

MRID Citation Reference

45910402 Hisgen, M. (2000) Determination of the Acute Effect on the Swimming Ability of the Water Flea Daphnia magna Straus: Ethylenethiourea (ETU): Lab Project Number: 00/0533/50/1: 2000/1017216: PCP05988. Unpublished study prepared by BASF Aktiengesellschaft. 27 p.

46020901 see
45910402 Hisgen, M. (2003) Reg No. 146099: Determination of the Acute Effect on the Swimming Ability of the Water Flea Daphnia Magna Straus: Final Report. Project Number: 00/0533/50/1. Unpublished study prepared by BASF Aktiengesellschaft. 25

p.

46462903 Palmer, S.; Kendall, T.; Krueger, H. (2001) Ethylene Urea: A 48

- Hour Static Acute Toxicity Test with the Cladoceran (Daphnia magna): Final Report. Project Number: 299A/114. Unpublished study prepared by Wildlife Internat ional, Ltd. 37 p. 

### 850.1025 Oyster acute toxicity test (shell deposition)

MRID Citation Reference

47474301 York, D. (2008) Ethylenethiourea

- Acute Toxicity to Eastern Oyster (Crassostrea virginica) Under Flow

- Through Conditions. Project Number: 13921/6102, 2007/02. Unpublished study prepared by EBDC/ETU Task Force. 66 p. 

### 850.1035 Mysid acute toxicity test

MRID Citation Reference

47441204 Soucy, K. (2008) Ethylenethiourea

- Acute Toxicity to Mysids (Americamysis bahia) Under Static Conditions, Following OPPTS Guideline 850.1035. Project Number:

### 74 13921/6103, 2007/03. Unpublished study prepared by Springborn Smithers Laboratories. 57 p.



### 850.130 0 72

- 4 Daphnid chronic toxicity test

MRID Citation Reference

46462901 Graves, W.; Mank, M.; Swigert, J. (1995) Ethylene Thiourea (ETU): A Flow

- Through
Life

- Cycle Toxicity Test with the Cladoceran (Daphnia Magna): Final Report. Project
Number: 129A/116, 94RC/0001. Unpublished study prepared by Wildlife International, Ltd. 122 p.



## 850.4400 Aquatic plant toxicity test using Lemna spp. Tiers I and II

MRID Citation Reference

47441203 Softcheck, K. (2008) Ethylenethiourea

- 7

- Day Toxicity Test with Duckweed (Lemna gibba) Following OPPTS Draft Guideline 850.4400. Project Number: 13921/6101, 2007/01. Unpublished study prepared by Springborn Smithers Laboratories. 69 p.



### 850.5400 123

- 2 Algal toxicity, Tiers 1 and II

MRID Citation Reference

46462904 Palmer, S.; Kendall, T.; Krueger, H. (2001) Ethylene Urea: A 96

- Hour Toxicity Test with the Freshwater Alga (Selenastrum capricornutum): Final Report. Project Number: 299A/116. Unpublished study prepared by Wildlife International, Ltd. 49 p.

46020902 see
45910403 Reuschenbach, D. (2000) Determination of the Inhibitory Effect on the Cell Multiplication of Unicellular Green Algae: Ethylenethiourea (ETU): Lab Project Number: 00/0533/60/1: 2000/1017191: PCP05997. Unpublished study prepared by
BASF Aktiengesellschaft. 28 p. 

### 850.7100 Data reporting for environmental chemistry methods

MRID Citation Reference

46623335 Tilting, N. (2004) Residues of Metiram and ETU in Potential Feed Items of Birds and Wild Mammals Following Application of Polyram WG (BAS 222 28 F) in Potatoes: (Final Report). Project Number: 136963, 13512075, 2004/1006523. Unpublished study prepared by BASF Aktiengesellschaft and Institut fuer Biologische Analytik und Consulting IBACON. 136 p.

157594 E.I. du Pont de Nemour s & Co., Inc. (1982) Manzate (IN

- 7331): Determination of Ethylenethiourea (ETU) Liquid Chromatographic Method: Method No: M20.1842(R). Unpublished study. 4 p.

45151401 Connolly, P. (2000) Independent Laboratory Analytical Method: Method for the Analysis of Ethylenethiourea (ETU) in Water by LC/MS/MS (MS 178.00) Revision 2:

### 75 Lab Project Number: 002

- 342: 00P

- 002

- 342: MS 178.00. Unpublished study prepared by Centre Analytica l Laboratories, Inc. 88 p. {OPPTS 850.7100}



### Non

- Guideline Study

MRID Citation Reference

42610001 Ruckert, E. (1992) Letter Sent to S. Lewis, dated Dec. 28, 1992: Regarding Ethylene thiourea 104 week chronic toxicity (feeding) study in rats: Source of information from final report RCC project number 256803. Prepared by EBDC/ETU Task Force. 3 p.

43641401 Weinberg, D.; Weiss, D. (1987) Response of the Maneb Data Task Force and Pennwalt Corporation to the Environmental Protection Agency's Initiation of Special Review of the EBDC Pesticides: (Risk Exposure Assessment). Unpublished study prepared by Fox, Weinb erg & Bennett. 28 p.

43641501 Weinberg, D.; Weiss, D. (1987) Response of Pennwalt Corporation to the Environmental Protection Agency's Initiation of Special Review of the EBDC Pesticides/Mancozeb: (Risk Assessment): (Includes "EBDC Special Review:
Toxico logical Issues"). Unpublished study prepared by Fox, Weinberg & Bennett. 51

p.

44418801 Waylett, D.; Slesinski, R.; Sert, M. et al. (1997) Acute Dietary Exposure and Risk Assessment: Ethylenebisdithiocarbamates (EBDCs) and Their Common Metabolite, Ethyle ne Thiourea (ETU): Lab Project Number: EBDC 97

- 01. Unpublished study prepared by Tas

- Environ. 95 p.

45225404 Hurt, S. (2000) Toxicity Endpoints and Reference Doses for Ethylenethiourea: Lab Project Number: 00R

- 1061. Unpublished study prepared by EBDC/ETU Task Force. 22 p.

45924404 Chernoff, N.; Kavlock, R.; Rogers, E.; et al. (1979) Perinatal Toxicity of Maneb, Ethylene Thiourea, and Ethylenebisisothiocyanate Sulfide in Rodents. Journal of Toxicology and Environmental Health 5: 821

- 834.

46268301 Arce, G. (2003) The Influence of Perinatal Exposure to ETU in the Development of Thyroid Effects and Other Critic al Toxicological Parameters. Project Number: 2/03/EBDC. Unpublished study prepared by EBDC/ETU Task Force. 20 p.

46319901 Ollinger, J. (2004) EBDC/ETU Task Force Response to U.S. EPA's Draft Science Chapter for the Environmental Fate and Ecological Risk A ssessment for Ethylenethiourea (ETU) Dated June 2, 2004. Project Number: EBDC/FQPA/2004/01. 38 p.

46480002 Ollinger, J. (2005) EBDC/ETU Task Force Response to U.S. EPA's Draft Science Chapter for the Environmental Fate and Ecological Risk Assessment for Ethylenethiourea (ETU) Dated October 20, 2004. Project Number: EBDC/FQPA/2005/01. Unpublished study prepared by EBDC/ETU Task Force. 24 p.

### 76 46480003 Ollinger, J. (2005) Ethylenebisdithiocarbamate Fungicides

- Benefits to United States Agriculture. Project Number: EBDC/FQPA/2005/03. Unpublished study prepared by EBDC/ETU Task Force. 261 p

47292002 Wuest, P.; Singh, H. (1983) Assessment of Zineb Residue Levels Through Dermal and Inhalation Exposures and its Major Metabolite [Ethylenethiourea (ETU)] in Biolog ical Fluids: Final Report. Project Number: 59/2421/0/2/012/0. Unpublished study prepared by Pennsylvania State University and Enviro

- Bio

- Tech, Ltd. 43 p.

47432128 Wang, G. (1988) Regulatory Decision Making and the Need for and the Use of Exposure Data on Pesticides Determined to Be Teratogenic in Test Animals. Teratogenesis, Carcinogenesis, and Mutagenesis 8:117

- 126.

48597301 Marty, M.; Chukwdebe, A.; McCoy, A. (2011) Exposure to ETU during Different Life Stages: Kinetic Considerations. Project Number: EO GRTS/TK. Unpublished study prepared by EBDC/ETU Task Force. 18p.

49254303 Thienpont, B.; Tingaud

- Sequeira, A.; Prats, E.; et al. (2011) Zebrafish Eleutheroembryos Provide a Suitable Vertebrate Model for Screening Chemicals that Impair Thyroid Hormone Synt hesis. Environmental Science & Technology 45(X):
7525

- 7532.

### 77 

## A ppendix B . SIP Output

Table 1. Inputs

Parameter Value

Chemical name Metiram
Solubility (in water at 25 o C; mg/L) 2

Mammalian LD 50 (mg/kg

- bw) 5000 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species

Mammalian NOAEL (mg/kg

- bw) 40 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species

Avian LD 50 (mg/kg

- bw) 2150 Avian test species mallard duck Body weight (g) of "other" avian species Mineau scaling factor 1.15

Mallard NOAEC (mg/kg

- diet) 50 Bobwhite quail NOAEC (mg/kg

- diet) NOAEC (mg/kg

- diet) for other bird species Body weight (g) of other avian species NOAEC (mg/kg

- diet) for 2nd other bird species Body weight (g) of 2nd other avian species

Table 2. Mammalian Results

Parameter Acute Chronic Upper bound exposure (mg/kg

- bw) 0.3440 0.3440 Adjusted toxicity value (mg/kg

- bw) 3845.8028 30.7664 Ratio of exposure to toxicity 0.0001 0.0112

Conclusion* Drinking water exposure alone is NOT a potential

concern for mammals Drinking water exposure alone is NOT a potential

concern for mammals

Table 3. Avian Results

Parameter Acute Chronic Upper bound exposure (mg/kg

- bw) 1.6200 1.6200 Adjusted toxicity value (mg/kg

- bw) 1116.3346 2.4806 Ratio of exposure to acute toxicity 0.0015 0.6531

Conclusion* Drinking water exposure alone is NOT a potential
concern for birds Drinking water exposure alone is NOT a potential
concern for birds

*Conclusion is for drinking water exposure alone. This does not combine all routes of exposure. Therefore, when aggregated with other routes ( i.e ., diet, inhalation, dermal), pesticide exposure through drinking water may contribute to a total exposure that has potential for effects to non

- target animals.

### 78 

## Appendix C . STIR Output



# Input

Application and Chemical Information

Enter Chemical Name Metiram

Enter Chemical Use

Is the Application a Spray? (enter y or n) y If Spray What Type (enter ground or air) ground Enter Chemical Molecular Weight (g/mole) 1088 Enter Chemical Vapor Pressure (mmHg) 7.60E

- 08 Enter Application Rate (lb a.i./acre) 2.4

Toxicity Properties

**Bird**

Enter Lowest Bird Oral LD 50 (mg/kg bw) 2150 Enter Mineau Scaling Factor 1.15 Enter Tested Bird Weight (kg) 1.58

**Mammal**

Enter Lowest Rat Oral LD 50 (mg/kg bw) 5000

Enter Lowest Rat Inhalation LC 50 (mg/L) 5.7 Duration of Rat Inhalation Study (hrs) 4 Enter Rat Weight (kg) 0.35



# Output

Results Avian (0.020 kg ) Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 4.45E

- 03

Maximum 1

- hour Vapor Inhalation Dose (mg/kg) 5.59E

- 04

Adjusted Inhalation LD 50 9.85E+00

Ratio of Vapor Dose to Adjusted Inhalation LD 50 5.68E

- 05 Exposure not Likely Significant

Maximum Post

- treatment Spray Inhalation Dose (mg/kg) 2.54E

- 01 Ratio of Droplet Inhalation Dose to Adjusted Inhalation
LD 50 2.57E

- 02 Exposure not Likely Significant



### Results Mammalian (0.015 kg ) Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 4.45E

- 03

Maximum 1

- hour Vapor Inhalation Dose (mg/kg) 7.03E

- 04

Adjusted Inhalation LD 50 3.39E+02

Ratio of Vapor Dose to Adjusted Inhalation LD 50 2.07E

- 06 Exposure not Likely Significant

Maximum Post

- treatment Spray Inhalation Dose (mg/kg) 3.19E

- 01 Ratio of Droplet Inhalation Dose to Adjusted Inhalation
LD 50 9.39E

- 04 Exposure not Likely Significant