2

Table of Contents

1 Executive Summary.............................................................................................................. 3

2 Introduction........................................................................................................................... 7

3 Use Characterization ............................................................................................................ 8

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

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

4 Conclusions from Previous 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 Metiram 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 Stressors 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 Summary

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 problem 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 overview 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 unacceptable or supplemental. The 

problems identified in these studies were mainly related to characterization/quantification of 

metiram residues. For example, identification/quantification of chemicals in the metiram 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 the 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 metiram active ingredient 

to which solubility is known (pre-determined by 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 guideline 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 835.400): A new guideline study for metiram in two 

water/sediment systems;

Aerobic soil metabolism (OCSPP 835.4100): A new guideline study for ETU in 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 possible identify the unextracted 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 duration. Due to the fact that there are 

transient species forming early it is recommended that shorter intervals are chosen for the first 

week of the study;

(2) The objective of metabolism 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 sediment 

following EFED un-extracted residues guidance1

.

ECM/ILV (OCSPP 835.6100): The registrant is requested to submit environmental chemistry 

method and associated independent laboratory validation (ECM/ILV) studies for determination of 

metiram and ETU in soil and metiram only in water.

Ecological Effects

The following uncertainties are identified for metiram:

Extent of toxicity to larval and juvenile honey 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 

introduction 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 freshwater 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-extracted 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 uncertain 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 residues 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 

CO2. 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 

ecotoxicity 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 actual oral route of exposure. Available records indicate 

the submission of an acute oral toxicity study with a passerine species for another Ethylene-bisdithiocarbamate (EBDC) chemical, mancozeb (canary, Serinus canaria, MRID 48515401). A 

preliminary review of this study indicates 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 the 

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 classified 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 less than 15% parent within a day, these transformation rates 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 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.

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 potential acute and chronic effects 

to individual adult and larval bees. 

A study examining the acute contact and acute oral toxicity to the adult honey bees is currently in 

review (MRID 49403401). There are no data available, however, to characterize the potential 

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 recommended 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 individual adult 

and larval bees. There 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, 2014)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). 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 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 LD50

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

3

http://www.oecd.org/chemicalsafety/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-tier 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 residues 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 the 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 registrant 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 larvae 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 and 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 protocol 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 

testing 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 C12H12N6S16Zn], is an ethylene bis dithiocarbamate (EBDC) non-systemic fungicide with 

protective action on contact. The dithiocarbamate group 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 (FRAC4

). 

 4 Fungicide Resistance Action Committee: URL: http://www.frac.info/docs/default-source/publications/frac-codelist/frac-code-list-2015-finalC2AD7AA36764.pdf (accessed June, 2015)
8

3 Use Characterization

3.1 Labelled Use

Metiram is registered for use on potatoes 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 management programs 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) and one 

Special Local Need (SLN Registrations under FIFRA Section 24 (c) (EPA registration number: 

FL980001). Metiram is formulated only as water dispersible granules (dry flowable “DF”) 

and applied as liquid spray using ground, aircraft, or through irrigation systems 

(chemigation). Table 1 contains a summary of all labeled uses.

Table 1 Metiram use patterns

Crop Use Pattern

Application Parameters 1

MSR MNA MTR MAI Notes

Apple 2.4 7 16.8 7

Aerial 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 applications may be 

combined or integrated

Potatoes 1.6 6 9.6 5 Aerial or Ground Foliar sprays and Chemigation

Ornamental in FL only (SLN) 2 1.6 10 16.0 7 Ground 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 labels 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 

apples. 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 against 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 tool for resistance management.

4 Conclusions from Previous Risk Assessments

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

(1) Environmental Fate and Ecological Risk Assessment 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 

Degradate of the Ethylene bis di-thio carbamate fungicides (EBDCs): Mancozeb, Metiram, 

and Maneb (Phase 3 Response),” dated June, 2005. The two documents were prepared by 

EFED for the Reregistration Eligibility Decision for Metiram (RED) (Document EPA 73-R05-017 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 recent risk assessments, including 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 previous assignments for the stressor of concern following new submittals 

including:

o Fate studies with better characterization/quantification of metiram residues;

o New ecological toxicity studies for ETU, the major degradate of metiram; and

o New sediment toxicity studies.
10

4.1 Ecological Risk Assessment 

As stated previously, the Agency has completed two main ecological risk assessments on metiram

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) and 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 Table 2.

Table 2. Summary of risk concerns identified for metiram in previous assessments*

Birds Mammals

Terr.

Plants

Terr.

Inverts Fish BCF

Aquatic 

Inverts

Aquatic 

Plants

Groundwater 

Contamination Persistence

Degradates 

of Concern

Yes Yes NA NA Yes NA1 No Yes Yes2 Yes3

The Metiram

Complex

* “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 KOW of 6-83; noting that no fish bio-accumulation study was submitted 2 Based on ETU, the degradate of concern of metiram which is characterized by high solubility and low KOC (288 

L/kg)

3 Based on only mineralization of the “Metiram complex” to CO2.

4.2 Drinking Water Exposure Assessments

Ethylenethiourea (ETU) is the common degradate of all Ethylene-bis-dithiocarbamates (EBDCs) 

fungicides including metiram. ETU, a group B2 carcinogen, was established to be the drinking 

water stressor resulting from the use of all EBDCs. 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 

dated August 11, 2006; DP Barcode: 397306 dated July 3, 2012; and DP Barcode: 420706 dated 

September 8, 2014).

For surface water, EDWCs were calculated using the linked PRZM and EXAMS simulation 

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/chronic EDWC was derived from community water system intake concentration of a 

targeted groundwater monitoring study conducted by the EBDC Task Force from 1999 to 2003. 

Targeted monitoring data were submitted under MRIDs: 45570301; 45708301; 45836401 and 

46145401. 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 Noncancer/Cancer chronicAcute 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 data, from this registration review for metiram and ETU will be considered for the 

determination of EDWCs for ETU resulting from metiram degradation. An updated drinking 

water assessment may be needed as part of the future Registration Review process. If a new 

drinking water assessment is needed, 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 chronic 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 section 303(d) of the Clean Water 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 aquatic benchmarks have been established only for 

ETU (Table 4). However, no acute non-vascular/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 life benchmarks 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 fish, toxicity value is usually the lowest NOEAC from a lifecycle 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 

EC50 or LC50 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} bimolecular and tri molecular 

cyclic anhydrosulfides and disulfides. The structure contains four monomer units and based on the 

molecular weight, it contains: 77.3% EBDC, 17% Zn+2 and 4.7% NH3. Hereunder is the 

chemical structure, formula, name and molecular weight.

Formula: C16H33N11S16Zn3; Molecular Weight= 1088.6 g mole-1; IUPAC Name: zinc 

ammoniate ethylene bis(dithiocarbamate) - poly[ethylenebis(thiuram disulfide)]; CAS Name:

tris [ammine-[ethylene bis(dithiocarbamate)]zinc(II)][tetrahydro-l ,2,4,7-dithiadiazocine-3,8-

dithione] polymer; and CAS Number: 9006-42-02; EPA PC code: 014601

The metiram polymer has a unique water solubility property as it decomposes in water within 

hours under acidic, 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 registrant, to equal 2 ppm. It appears that solubility is 

dependent on the source of the metiram and that the 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 (NH3)

N

N

H

H

Metiram

C

C

S

S

N S

N

H

S 3 H X

X>1
13

 Metiram Monomer (EBDC anion) + Zn+2

 Figure 1 Expected decomposition/hydrolysis process for metiram in water

 

The length of the polymer chains, of the metiram 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 susceptibility to the 

process of decomposition into shorter or monomeric chains by solution/hydrolysis in water.

In the field, metiram is expected to be applied into moist plant foliage and reach, upon application 

and later due to wash-off, a moist soil system. 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 metiram into its 

monomeric units is expected to occur in soil and water/sediment. The maximum single application 

rate of metiram ranges from 1.6 to 3.6 lbs. a.i/acre. Upon application, the maximum expected 

concentrations of metiram in the soil system will probably be in the range of <0.8 to <1.8 ppm 

depending on how much of the applied reaches 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 important at these concentrations 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 lower than moist conditions.

Based on the fact that metiram, as a polymer, is expected to be short lived in the environment. It 

is necessary to obtain exposure data for metiram as well as the residues forming in soil and 

water/sediment systems following the decomposition/hydrolysis/process. 

(a) Physical Chemical Properties and Abiotic Transformation

Physical and chemical properties and abiotic transformation of metiram are included in Table 5.

Table 5 Physical/chemical properties and abiotic transformation of metiram

 

 

 

N C

N

H

H

S -

N

C S -

N

Property Value Reference 1

n-octanol-Water 

Coefficient (KOW) 6 to 83; based on its reported log of 0.78 to 1.92 Product 

Vapor Pressure 7.5 x 10 Chemistry -8 torr @ 25 oC

Henry's Law constant 5.4 x10-8 atm. m3 mole-1 @ 25 oC (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 oC; Uncertain values 2 001467-64 (S)

Metiram Polymer
14

Hydrolysis data suggest that abiotic hydrolysis appears to be fast and causes degradation of the 

monomeric units of metiram that is expected to form initially upon dissolving the polymer in water.

(Table 5). Therefore, the fate of metiram polymer chains appear to be affected significantly by 

two processes. The first process is 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, ETU, 

EU and HYD). Although the study gives certainty that metiram parent is highly affected by 

hydrolysis, there are many uncertainties in this study that prevent accurate conclusions on the 

hydrolysis profile for polymeric metiram 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 

metiram active ingredient to which solubility is known (pre-determined by a guideline study) 

starting with concentration below this pre-determined solubility.

Furthermore, data in Table 5 indicate that metiram is not expected to partition into the air from 

dry/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-concentration 

potential for metiram 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 data 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 data 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 its

solubility of 2 ppm. Additionally, suspensions were prepared by sonication that is expected to reduce particle size which may 

shorten determined half-lives. Additionally, metiram parent was determined by the CS2 method which is expected to result in 

longer half-lives because most of the degradation products contain sulfur that produces CS2 resulting in higher metiram 

concentrations and longer half-lives.

3 These 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 DT50) 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 DT50) 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 DT50) 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 DT50) 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 

questionable2

;

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; Unidentified (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 Me-OH) declined to 38% @ EOS; noting that Max 

after double extraction with Me-OH and EDTA was 48% 

@ 14 d then declined to 32% @ EOS

Mineralization to CO2: 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, 

CO2 (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 CO2 (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 oC (100 

day study; noting that the 

sediment was anaerobic)

0.5 days (Observed DT50) 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 DT50) 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 CO2: 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 CO2: Max 8% @ EOS 459334-01 (A)

Anaerobic Aquatic t 1⁄2 @ 25 oC 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 [14C] metiram parent degraded within 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 CS2

5

. Aerobic soil studies appear to demonstrate the effect of the following 

processes on the polymeric chains of metiram:

 5 In reviews for submitted studies for EBDC fungicides, EFED noted that CS2 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 soil/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 CS2 forming compound on metiram determination was acknowledged 

for structures containing two sulfur atoms bound to the same carbon atom such as EBIS (MRID 459069-01).
17

• Decomposition/hydrolysis of the polymer chains of metiram, by water, into EBDC ions; and 

transformation of the EBDC ions into a residue containing several degradation products by

hydrolysis/biotransformation;

• Formation of substantial amounts of un-identified/un-extracted residue (UER); and

• Mineralization of the metiram residues into CO2.

The process of decomposition/hydrolysis appears to start in the step of preparing the stock solution 

of metiram polymer as indicated by observation of transformation products at time zero. 

Hydrolysis/biotransformation appear to cause transformation of the EBDC units into the metiram

residues consisting of the following major/minor transformation products: EBIS, TDIT, ETU, EU, 

Carbimid and un-identified degradates. Partitioning of significant amounts of the metiram residues

into the soil resulted in the formation of substantial amounts of an UER. Finally, mineralization 

of part of the metiram residues resulted in production of CO2.

Observed decomposition/degradation in two aerobic water/sediment systems were similar to that 

observed in the soil systems. It appears that processes involved in these systems are similar to 

those suggested earlier for the aerobic soil systems. In the two systems, parent decomposes rapidly 

(within a day) with the formation of the metiram residues consisting of the following degradates:

EBIS (with minor TDIT), ETU, EU, UER and CO2. 

(c) Mobility

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

were based on radioactivity adsorbed to the soils used in these two studies. This is because metiram

degraded very quickly forming the metiram residues. Therefore, calculated Koc values are for 

metiram residues. Average adsorption coefficient data suggest that the metiram 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, 

determined 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 metiram 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 Silt loam soil from MS (O.M= 1.0%, 

pH= 7.5 and CEC= 10 meq/100g); and

1,738 mL/g for a Clay soil from MD (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 DT50 of 143 days while a study conducted in California on the same crop reported

a DT50 of 20 days (MRIDs 414408-01/02). For the same studies, reported a DT50s 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 these studies. 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 requirements 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 products 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 biotransformation 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 (UNID). 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-extracted (UER). 

Data also show that part(s) of the metiram residues are expected to be mineralized into CO2

(Figure 2).
19

Figure 2 Transformation profile for metiram in soil and aquatic systems (refer to abbreviations 

below). 

 EBDC anion + Zn+2

 EBIS (DIDT); Carbimid and TDIT, respectively (Transitional Degradates)

 

NH

NH

C S

 

NH

NH

C O

 ETU + EU + UN-ID + UER

 

Metiram Residues

 CO2

· EBIS= Ethylene bis isothiocyanate sulfide (5,6-Dihydro-3H-imidazol(2,1-C)-1,2,4-dithiazole-3-thione ; 

· ETU= Ethylene thio urea (2-Imidazolidinethione); CH3H6N2S; CAS No.:96-45-7; Mol. Wt.: 102.16 g mole-1

· EU= Ethylene urea (2-Imidazolidinone); CH3H6N2O; 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

N S

C S

C

S

NH

S

 

N

C

C

NH2

S

 

N

C

C

C

N

N

S

S

N

Metiram 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 systems.

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 these systems, a suite of degradates (EBIS, ETU, EU and unidentified degradates; represented 

by the extractable radioactivity) forms and reaches 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 stable 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 degradates.

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 lines 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 

 UER 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 continues 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. The 

maximums for these two degradates occur consecutively at 1 day 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 halflives (0.2 day). 

Figure 6 contains a summary of the observed total degradates and UER in two aerobic water/

anaerobic sediment soil systems. 

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 unidentified/un-extracted residues (UER). The UER 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 profile of the various constituents of the observed 

degradate suite in the water/sediment systems.

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 following 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 maximum, 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 1st order half-life is 71 days in the river system 

and 264 days in the pond system. ETU degradation pattern is similar in timing/intensity to 

evolved CO2 suggesting bio-degradation by mineralization;

(c) EU appears to be maintained at a level of 4-6% throughout the study; and

(d) UN-ID appears 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 EBDC fungicides (EBDCs) including metiram. As 

a metiram 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 metiram 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 found to be converted to 

ETU). Second, ETU is produced from hydrolytic/biotic degradation of parent metiram 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 of transient species in pore water/water bodies and 

possibly from soil/sediment bound residue of metiram. Rapid hydrolysis/biotransformation of 

metiram parent and/or residues are expected to be the major processes that control ETU production 

in soils and water bodies. In addition, slow biotic degradation of un-extracted (UER) metiram

residues may also contribute to the production of ETU in the long term. It is noted that the slow 

production of ETU from metiram UER is uncertain as the identity of these residues are unknown. 

As stated above, ETU is produced mainly from decomposition/hydrolytic/biotic degradation of 

parent metiram. Laboratory data on hydrolysis of metiram 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 hydrolysis study is requested for metiram in which all degradation products, 

including ETU are tracked. 

In the aerobic soil system, hydrolytic/biotic degradation of parent metiram 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 decline to <LOQ at day 14. This data is summarized in Figure 8.

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

Similarly ETU was observed to be produced in the aerobic aquatic systems from hydrolytic/biotic 

degradation of parent metiram. In these systems, maximums observed was ranged 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 production. 

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 (C3H6N2S)

n-octanol-Water Coefficient (KOW) 0.2 MRID 406510-01 (A)1

Vapor Pressure 5.01x10-3 torr Neely WB & Blau GE2

Henry's Law constant 3.4X10-7 atm. m3 mole-1 Meylan WM & Howard 

PH3

Water Solubility 20,000 ppm @ 20 o

C and 90,000 ppm @ 60 oC 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 absorbance 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 relatively low Henry’s Law 

constant suggests possible low volatilization of ETU into the air from wet soil and water. ETU has 

a low Kow 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 CO2

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 oC

From Parent Study: 

71 days (Single 1st 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 1st 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 oC

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 90th 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 important to note that slightly longer 90th 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) ETU degraded under aerobic water/anaerobic sediment systems with a single 1st order half-life 

of 71 days in the river system and a single 1st 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 guidance6

.

(c) Mobility

Data for mobility were estimated from a supplemental adsorption/desorption study (Table 10). It 

is noted that there were problems with this study such as the possibility of occurrence of 

degradation of ETU before conducting the experiment. The study was classified as supplemental 

following registrant submittal of data suggesting that the applied test substance included 

significant quantities 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 

Koc= 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 (DT50s) of 1 to 6 days and <7 days were observed in fine sand and silt loam 

field soils in parent metiram studies (Supplemental studies: Accession Nos. 002552-29 and 

000889-23).

(e) Bio-concentration

ETU is associated with very low KOW values of 2. Fish bioaccumulation study was previously 

waived for ETU based on the expected low bio-concentration as indicated from KOW.

(f) Transformation Products

ETU is a result of abiotic/biotic degradation of metiram/metiram 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 biodegradation in soils and to a lesser extent in biologically active 

aquatic media. Many 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)-Imidazoledione; 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-imidazol2-yl)-imidazolidin-2-thion; CAS No. 484-92-4); EDA (Ethylenediamine) and CO2. 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 Concern 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 CS2 ) 

Data in Figure 9 suggest that chemical species that may reach aquatic systems by run-off from the 

soil include significant amounts of the UER and lesser 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 chemical species with different concentrations and at different timeline as shown in Figure 10, below.

Figure 10 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 10 suggest that the constituents of the metiram residues will be dominated with undegraded parent from drift alone, transient species (EBIS, Carbimid and TDIT), ETU and EU at 

the short term and EU and the UER at the long term. Therefore, aquatic 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 11 below alongside the endpoints derived from parent metiram studies. For 

the transient degradate EBIS, there is no registrant submitted data available, and therefore the 

structural activity relationship (SAR) tool ECOSAR (v 1.1) was employed to estimate the toxicity 

to taxa where 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 orders of magnitude less toxic than 

parent metiram. As shown in Table 11, 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 registrant submitted and ECOSAR estimates of the various degradation 

product of metiram

Taxa 

Stressor

(data source)

FW Fish 

LC50

FW

Invert 

LC50

FW fish 

NOAEC

FW invert 

NOAEC

E/M

fish 

LC50

E/M 

invert

LC50

E/M Fish 

NOAEC

FW 

Green 

Algae

Parent metiram

(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

EBIS

(Thiocarbamate, di 

(substitute ECOSAR 

class)

0.18 0.62 0.015** 0.041** 0.10
32

Taxa 

Stressor

(data source)

FW Fish 

LC50

FW

Invert 

LC50

FW fish 

NOAEC

FW invert 

NOAEC

E/M

fish 

LC50

E/M 

invert

LC50

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 243891 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 days, total parent metiram is approximately 13% while 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 days (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 unextracted 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 unextracted 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 these 

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 registrant 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 organisms):

• 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 degradation 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 behavior 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 Receptors

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 growth 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 metiram 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 literature 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 acute 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 LC50 endpoints range from 0.23 to >160 mg a.i/L, which classifies 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 with the bluegill sunfish, although the LC50 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 

increased. 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 life 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 design. 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 early life 

stage study with the fathead minnow (MRID 48246303) is in review.

Available data indicate that metiram has a 96-hr LC50 of >0.67 mg a.i/L on an acute exposure basis 

to estuarine/marine fish. There were no reported clinical signs of toxicity during 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 

EC50 of 0.63 mg a.i/L. Clinical signs of toxicity included lethargy and trapped at the surface of 

the tank with pale discoloration. A chronic life cycle study with Daphnia magna exposed to flow 

through conditions of metiram has been submitted and is currently in review (MRID 48392001). 

Available 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 LC50 values 

ranging from 0.025 – 0.83 mg a.i/L. There were no clinical signs of toxicity 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 48392002)

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 EC05 in order to estimate risk to listed aquatic non-vascular 

plants. Therefore, the 96-hr EC50 and EC05 are 0.015 and 0.003 mg a.i/L, respectively. 

Table 12. Summary of the most sensitive endpoints from aquatic toxicity studies for metiram

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 fish1 Acute - TGAI

Rainbow trout 

(Oncorhynchus 

mykiss)

96-hr LC50: 0.23 

mg/L (0.14 –

0.93; 2.23)

Highly toxic 43525001

(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 EC50: 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 LC50: 

>0.67 mg/L 

(N/A; N/A)

Highly toxic3 48151303 

(Acceptable)

Estuarine/marine 

invertebrates

Acute – TGAI

Mysid shrimp 

(Americamysis 

bahia)

96-hr LC50: 0.025 

mg/L (0.019 –

0.033; 2.64)

Very highly 

toxic

48151304

(Acceptable)

Acute - TGAI

Eastern oyster

(Crassostrea 

virginica

96-hr EC50: 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)

Sedimentdwelling 

invertebrates

Subchronic 

(10-day) 

spiked 

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 

pelliculosa)

96-hour EC50 

(Biomass): 0.015 

mg/L (0.012 –

0.019; N/A)

96-hr EC05: 0.003

μg/L

-- 47645918

(Supplemental)

1 Freshwater fish may be surrogates for aquatic-phase amphibians. 2 (95% confidence intervals; slope) if available

3Although 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 endpoints from aquatic toxicity studies for the metiram degradate ETU

Taxonomic 

Group (study 

type)

Surrogate Species

Toxicity Value (all units in 

terms of measured active 

ingredient)2

Acute

Toxicity 

Classification

Source

(Classification)

Freshwater fish1

(acute toxicity) 

Rainbow trout

(Oncorhynchus 

mykiss)

96-hr LC50: >502 mg/L

(N/A; N/A)

Practically 

non-toxic

45910401

(Acceptable)

Bluegill sunfish

(Lepomis 

macrochirus)

96-hr LC50: >988 mg a.i/L Practically 

non-toxic

47441202

(Acceptable)

Freshwater 

invertebrates

(acute toxicity) Water flea 

(Daphnia magna)

48-hr EC50: 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 LC50: >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 LC50: 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 EC50 (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 EC50: >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

There 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 algae, 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 Species1 Toxicity Value1 AcuteToxicity 

Classification

Source

(Classification)

Freshwater fish2

(acute toxicity) 

Rainbow trout

(Oncorhynchus mykiss)

96-hr LC50: >122 mg/L

(N/A; N/A)

Practically 

non-toxic

46462902

(Acceptable)

Freshwater 

invertebrates

(acute toxicity) 

Water flea 

(Daphnia magna) 48-hr EC50: >985 mg/L Practically 

non-toxic

46462903

(Acceptable)

Aquatic plants

Freshwater green algae 

(Pseudokirchneriella 

subcapitata) 

96-hr EC50: >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 (Colinus virginianus, MRID 

40656901), there were no mortalities or clinical signs of toxicity observed during the course of the 

study. The LD50 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 LC50 

determined to be 3712 mg a.i/kg-diet. Clinical signs of toxicity in the bobwhite study included 

wing droop, depression, and labored respiration at the highest treatment concentration (4640 mg 

a.i/kg-diet). Similar effects 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. 

An acute oral toxicity study with metiram on the Norway rat (Rattus norvegicus) (MRID 

40497002) indicated that metiram is practically non-toxic to mammals on an acute exposure basis 

with an LD50 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 performance 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 weight. The most 

sensitive dicot was tomato, based on significant effects to percent emergence. For wheat, the 

NOAEC and EC25 were determined to be 0.37 and >2.86 lbs a.i/A, respectively. For tomato, the 

NOAEC and EC25 was determined to be 0.11 and >2.86 lbs a.i/A. An EC25 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 treatment group (2nd lowest) is the EC25

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

In the vegetative vigor study, 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 EC25 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, and 4.9, respectively. The EC25 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 15. 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)

Birds1

Acute Oral

Bobwhite quail 

(Colinus 

virginianus)

21-day LD50: 

>2250 mg/kgbw

Practically 

non-toxic

40656901

(Acceptable)

Subacute dietary

Bobwhite quail 

(Colinus 

virginianus)

8-d LC50: 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 

LOAEC

(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 LD50 

>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

EC25 > 2.86 

lbs/A

NOAEC (dry 

weight) = 0.37 

lbs/A

--

47645915

(Acceptable)

Dicot – Tomato

EC25 : >2.86 lbs 

a.i/A 

NOAEC

(percent 

emergence) = 

0.11 lbs/A

Vegetative Vigor 

(Tier II)

Monocot -

None

EC25 >3.3 lbs

a.i/A 

NOAEC = 3.3 

lbs a.i/A 47645916

(Acceptable)

Dicot - None

EC25 >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.

3An 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 change 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 oral 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)

Birds1

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)

LC50 > 5620 mg/kgbw (N/A; N/A)Practically nontoxic48417801

(Acceptable)

Mallard duck

(Anas 

platyrhynchos)

LD50 > 5620 mg/kgbw (N/A; N/A)Practically nontoxic48417802

(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 or 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 exposure. 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 

were 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 incidents involving 

metiram. The incident was 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 azinphosmethyl, 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 metiram indicate that direct spray, spray 

drift, and runoff (mainly in events accompanied by erosion), represent potential transport 

mechanisms of metiram residues to aquatic and terrestrial organisms. Leaching to groundwater is 

an important pathway for ETU, the drinking water degradate of concern (ETU).

Other Exposure Pathways to Terrestrial Species

Drinking Water Exposure

The Screening Imbibition Program (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 LD50 >2150 mg a.i/kg-bw) and chronic avian toxicity endpoint (mallard 
42

duck NOAEC of 50 ppm) and the most sensitive acute and chronic mammalian toxicity endpoints 

(Norway rat LD50 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 pathway 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 contribute 

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 contribute 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 Screening Tool for Inhalation Risk (STIR v.l.0, November 19, 2010) was used to calculate an 

upper bound estimate of exposure using metiram’s vapor pressure (7.50E-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 (mallard duck acute oral LD50 = >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 LD50 = >5000 mg a.i/kg-bw and inhalation LC50 = >5.70 mg/L). 

Based 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 of 

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. However, 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 KOW 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 ecological 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 metiram.

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 

identified 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 with 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 implement 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 specific 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 shared 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 Approaches 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 

Approaches 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 effects 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 metiram 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 methods 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 

11.1Environmental Fate

Due to the complex nature of polymeric metiram and the state of science when some of the 

studies were conducted, difficulties were observed in these studies including:

(1) Parent degradation in the preparation steps of parent for the experiments;

(2) High percentage of the unidentified radioactivity remained unextracted 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 ETU 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 unidentified residue (possibly monomeric species); and

(5) Particle size reduction and presence of metal ions (that may replace zinc ion in the structure) 

are thought to increase hydrolytic decomposition and degradation rate.

The Agency understands 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);

001619-38 (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 Kow 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 Not at this time

835.6100 Terrestrial field dissipation

002552-29 

And 000889-23 Supplemental No

850.1730 Fish bio-concentration Waived because ETU Kow 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 assessment. 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 passerine 

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 assessment. 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 that parent metiram is shown to rapidly degrade to less than 

15% parent within a day, these transformation rates are derived from soil metabolism studies. It 
47

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

practices 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 above beginning on page 5 of this assessment with regards to the data 

needs identified relating to honey bees.

Table 19. 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

44301102 Invalid N/A --

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 cyclesaltwater 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

Nonguideline 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 Marine 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 22. 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 LD50 <11 μg 

a.i/bee). 

850.6200 Earthworm 

Subchronic 

Toxicity

No data available No --

Nonguideline 

study

Honey bee adult 

chronic oral 

toxicity 

No data available

Yes

Studies are needed as part of 

the tiered pollinator risk 

assessment approach.

Nonguideline 

study

Honey bee 

larvae acute 

oral toxicity

Nonguideline 

study

Honey bee 

larvae chronic 

oral toxicity

Yes

Nonguideline 

study (Tier 

2)

Field trial of 

residues in 

pollen and 

nectar 

Yes

850.3040

(Tier 2 or 

3)

Field Testing 

for Pollinators Yes

Nonguideline

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 23. 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 developing 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.oecdilibrary.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 data 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 the 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 are 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, pesticide residues may be transferred to pollen and/or nectar of treated plants and 

subsequently brought back to the hive. Therefore, potential chronic effects to 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 assist 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 determine the chronic oral toxicity of this compound to adult 

honey bees 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 guidances discusses Tier I laboratory-based chronic oral 

toxicity studies of individual adult honey bees 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. Although study design 

elements for the chronic 10-day oral toxicity test with honey bees are similar to the OECD TG 213 acute 

oral toxicity test (http://www.oecdilibrary.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 initiating the test.

Practical Utility of the Data

How will the data be used?

The Tier 1 chronic toxicity data 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 nonlisted terrestrial invertebrates, including pollinators, from chronic oral 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 terrestrial 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 result 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 of pesticide products to comply 

with FIFRA and the ESA, and could result in use restrictions. 

Study Title: Honey Bee Larvae Chronic Oral Toxicity

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 the 

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 information 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 initiating the test. 

Practical Utility of the Data

How will the data be used?

The Tier 1 chronic toxicity data 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 bee 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 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. 
54

Study Title: Semi-field Testing for Pollinators (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 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 and may 

adversely affect developing brood (egg, larvae, and pupae) and adult bees. Screening-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 

brought 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 residues 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 information 

on honey bee colony studies under semi-field conditions can be found in the OECD Guidance 75 

(http://www.oecd.org/officialdocuments/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 screeninglevel (Tier I) laboratory-based studies 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 field-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 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 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 Pollinators (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 exposed 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 effects 

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 spiked 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 bees 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/pollinator-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 

pollinators 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 studies 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.

How 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 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. 
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 applications (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 application 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/pollinatorrisk-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 data will be used to refine conservative 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 be 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 threatened 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 restrictions. 
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 the 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 Project 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 

Polyram 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 by 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 Schneider, 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: 

[Addendum]. 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 Prepared 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 - Complex: 

[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 Laboratories 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 Metiramcomplex. Unpublished study prepared by Fraunhofer Institut fuer Umweltchemie 

und Oekotoxikologie. 93 p. 
60

40576403 O’Grodnick, J.; Asshauer, J. (1988) HOE 070542—Photodegradation Studies 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 

XenoBiotic 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: Supplement to. Unpu- 61lushed 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 and 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 Rotational Crop Study: Lab Project Number: 2503. Unpublished study prepared 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, sevin, polyram, phygon and systox from apple orchard soil. Bulletin 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 Enviro-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 Metabolism 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 Analytical 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. (DER 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 Bio-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-Chemistry 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.

4515464-01

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 Ethylenethiourea 

(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 Monitoring 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 Number: ETU-2000-01: ETU- 0202: 6942. Unpublished study prepared by LFR Levine-Fricke, 

Enviro-Test Laboratories, and Morse Laboratories 366 p. 13-Jan2003

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. EPA'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 Metiram 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., submitted 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.; CDL: 

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 FMC 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 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

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 Aktiengesellschaft. 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.

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.

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-8817= 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., Philadelphia, 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. Unpub- 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. Unpublished 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. Unpublished 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. Unpublished 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 unknown admin. no.; prepared by Industrial BioTest 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 BioTest Laboratories, Inc., submitted by FMC Corp., Philadelphia, Pa.; CDL: 105214-

A) 

850.1010 72-2 Acute Toxicity to Freshwater Invertebrates

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 Corp., 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 Acute 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 FlowThrough 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 submission 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 FlowThrough 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 Aktiengesellschaft. 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. 

Unpublished 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 prepared 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: 2002/1005264. 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 LifeCycle 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 bahia). 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 (Pimephales 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 toxicity, 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 International, 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 pelliculosa). 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 the 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 (Skeletonema 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, 

Wilmington, 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. Unpublished 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 Registration 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 Reference

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 Aktiengesellschaft. 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 International, 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.

850.1300 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 Nemours & 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 Analytical 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, Weinberg & 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: 

Toxicological 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, 

Ethylene 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 Critical 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 Assessment 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 

Biological 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: EOGRTS/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 Synthesis. Environmental Science & Technology 45(X): 

7525-7532.
77

Appendix B. SIP Output

Table 1. Inputs

Parameter Value

Chemical name Metiram

Solubility (in water at 25oC; mg/L) 2

Mammalian LD50 (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 LD50 (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 LD50 (mg/kg bw) 2150

Enter Mineau Scaling Factor 1.15

Enter Tested Bird Weight (kg) 1.58

Mammal

Enter Lowest Rat Oral LD50 (mg/kg bw) 5000

Enter Lowest Rat Inhalation LC50 (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/m3) 4.45E-03

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 5.59E-04

Adjusted Inhalation LD50 9.85E+00

Ratio of Vapor Dose to Adjusted Inhalation LD50 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 

LD50 2.57E-02 Exposure not Likely Significant

Results Mammalian (0.015 kg )

Maximum Vapor Concentration in Air at Saturation 

(mg/m3) 4.45E-03

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 7.03E-04

Adjusted Inhalation LD50 3.39E+02

Ratio of Vapor Dose to Adjusted Inhalation LD50 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 

LD50 9.39E-04 Exposure not Likely Significant