OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION

 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON D.C., 20460 

 

PC Code: 084701 

MEMORANDUM DP Barcode: 422819, 422850 

DATE: October 22, 2014 

SUBJECT: Response to the Initial 60-Day Public Comment on: “Registration Review: Draft 

Problem Formulation for Environmental Fate, Ecological Risk, Endangered 

Species and Human Health Drinking Water Exposure Assessments for Etridiazole 

(05/06/14; PC Code 084701; DP Barcode 417576)” 

TO: Margaret Hathaway, Chemical Review Manager 

 Tom Myers, Team Leader 

 Risk Management and Implementation Branch II (RMIB II) 

 Pesticide Re-evaluation Division (7508P) 

FROM: Karen Milians, Ph.D., Chemist 

 Catherine Aubee, Biologist 

 Environmental Risk Branch IV 

 Environmental Fate and Effects Division 

 Office of Pesticide Programs 

REVIEWED 

BY: Jim Carleton, Ph.D., Senior Scientist

 Thomas Steeger, Ph.D., Senior Science Advisor 

 Environmental Risk Branch IV 

 Environmental Fate and Effects Division 

 Office of Pesticide Programs 

APPROVED 

BY: Sarah Winfield, Acting Branch Chief 

 Environmental Risk Branch IV 

 Environmental Fate and Effects Division 

 Office of Pesticide Programs 

The Environmental Fate and Effects Division (EFED) has reviewed the public comments on the 

Preliminary Work Plan for Registration Review of etridiazole1

, including the draft problem 

																																																																		 1

 Docket ID Number EPA-HQ-OPP-2014-4014 
Page 2 of 10 

formulation2

 for environmental fate, ecological risk, endangered species and human health 

drinking water exposure assessments. Comments received from the following stakeholders are 

addressed in this response: 

 MacDermid Agricultural Solutions (formerly Chemtura Corporation, registrant) (August 

19, 20123) 

 Physician’s Committee for Responsible Medicine (PCRM) (August 25, 20134) 

Additionally, an upgrade request submitted by MacDermid Agricultural Solutions (MRID 

49460901) is addressed in this document. 

In the following sections, the specific comment is summarized in italics and is then followed by 

EFED’s response. 

1. MacDermid Agricultural Solutions (formerly Uniroyal Chemical Company, Inc.), 

regarding MRID 43504305:

a) Upgrade request, submitted in MRID 49460901: “First, the solvent extraction scheme for 

soil, namely acetonitrile: 1% ammonium hydroxide in water (4:1), was able to effectively 

extract etridiazole from soil. That is, greater than 98% of the applied radioactivity at Day 

0 was extractable from the water/soil system and the extractable radioactivity 

corresponded to etridiazole. Only 1% of the applied radioactivity remained in the postextracted solids following extraction. Thus, the solvent used in the study was, in fact, 

appropriate to achieve quantitative extraction of etridiazole from soil. 

Hydrosoil-bound residues were indeed significant following extraction. Therefore, bound 

residues from two representative sampling intervals (Day 60 and Day 179) were 

additionally extracted with "stronger" solvents in an attempt to remove more radioactive 

residues. These samples represented sampling intervals, which were widely, spaced 

during the incubation period and also represented essentially maximum values for bound 

residues. Initially, the samples were extracted with acetonitrile:water:acetic acid 

(80:20:2.5) for 4 hours. Less than 3.5% of the applied dose was extractable from either 

sample. Analysis of the extracts from this solvent mixture showed less than 0.3% of the 

applied dose corresponding to etridiazole. The samples were then heated at reflux 

conditions with 0.25 N hydrochloric acid for about 1 hour. Despite this very rigorous 

extraction attempt, less than 10% of the applied dose was released. Of that released, only 

about half could be partitioned into ethyl acetate. Therefore, the 3-step extraction scheme 

indicated that, (1), etridiazole could be extracted from hydrosoil quantitatively with the 

initial solvent (acetonitrile:1% ammonium hydroxide in water (4:1) and (2), even 

stronger extraction solvents using more rigorous conditions were not able to remove 

more appreciable amounts of bound radioactive residues. Thus, it can be concluded that 

etridiazole, in an anaerobic and aquatic environment degrades quickly, forms significant 

																																																																		 2 US EPA 2014 Registration Review: Draft Problem Formulation for Environmental Fate, Ecological Risk, and Endangered Species, and Human 

Health Drinking Water Exposure Assessments for Etridiazole (PC Code 084701; DP Barcode 417576). From: C. Aubee and K. Milians, 

Environmental Fate and Effects Division; To: M. Hathaway and T. Myers, Pesticide Re-evaluation Division; 05/06/2014. 3

 EFED presumes that the actual date of correspondence is August 19, 2014, since it was submitted in response to the Preliminary Work Plan 

(June 25, 2014). 

4

 EFED presumes that the actual date of correspondence is August 25, 2014, since it was submitted in response to the Preliminary Work Plan 

(June 25, 2014).
Page 3 of 10 

amounts of soil-bound residues, and slowly those residues are microbially mineralized to 

carbon dioxide. 

A table summarizing the pH, redox and dissolved oxygen values is provided by the 

laboratory that conducted this study (Table 1). Collection of these data were mentioned 

in the report (p. 15) but not actually provided per se. These data indicate that dissolved 

oxygen concentrations are quite low, ranging from 0 - 0.7 mg/L (ppm), and clearly are 

indicative of an anaerobic environment. Furthermore, the redox measurements 

throughout the incubation period ranged from 14-109 mv, also indicative of a reducing 

environment. For instance, microbially mediated iron reduction (transformation of ferric 

ion to ferrous ion) indicative of environments that are anaerobic, become prominent 

when the oxidation-reduction potential falls below about 200 mV (see Introduction to Soil 

Microbiology, Martin Alexander, Second Edition, Krieger Publishing Co., Malabar, 

Florida, 1991, p.375 -- 376). Thus, these two parameters, namely, dissolved oxygen and 

redox potential, indicate that anaerobic conditions were maintained during the 

incubation period.” 

 EFED’s response: 

In preparing its data evaluation record (DER), the Environmental Fate and Effects 

Division (EFED) considered the information referred to in this comment, which was 

provided with the study report. The comment itself provides no new information, and 

EFED concludes that there is a lack of a compelling rationale for upgrading the study. 

The following deficiencies of the study are reiterated: 

1. EFED agrees that at day zero 98% of etridiazole was effectively extracted from 

soil. However, there is a concern with extractions at other sampling times when 

the recovery of etridiazole was considerably lower (sampling day 7-179 days 

post-treatment, 40.8-58.1% of the applied, respectively). Additional extractions 

should have been performed with sodium hydroxide and with other solvent 

systems in an attempt to recover a greater portion of the [14C] residues for 

characterization. In the absence of such an effort, it cannot necessarily be 

concluded that, as asserted in the comment, etridiazole in an anaerobic aquatic 

environment degrades quickly to form soil-bound residues, which are in turn 

ultimately mineralized. 

2. The redox potential in the study (range: 14 - 109 mV) was relatively high, thus it 

cannot be concluded that the test system constituted an anaerobic aquatic 

environment as specified per OCSPP Guideline 835.44005

, i.e., “the sediment 

and water are regarded as anaerobic once the redox potential (Eh) is lower than -

100mV.” 

Further deficiencies of the study are summarized in the DER for the study (MRID 

43504305). 

																																																																		 5

 USEPA. 2008. Fate, Transport and Transformation Test Guidelines. OCSPP 835.4400. Anaerobic Aquatic Metabolism. Office of Chemical 

Safety and Pollution Prevention formerly the Office of Prevention, Pesticides and Toxic Substances (7101) EFA 712-C-08-019. 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0152-0039 
Page 4 of 10 

2. MacDermid Agricultural Solutions, Inc. 

a) Guideline No, 850.1350 Mysid Chronic Toxicity Test 

MacDermid Agricultural Solutions Inc. is evaluating the etridiazole labels to update the 

language to avoid application near estuarine/marine invertebrate habitat. 

EFED’s response: 

There are currently no data available to address uncertainties associated with the potential for 

adverse effects to estuarine/marine fish and invertebrates since chronic data are not available 

for estuarine/marine invertebrates. As stated in 40 CFR Part 158.6606

, aquatic invertebrate 

life cycle data for a saltwater species are required if a product meets any of the following 

conditions: 

i. Intended for direct application to the estuarine or marine environment, 

ii. Expected to enter this environment in significant concentrations because of its 

expected use or mobility patterns. 

iii. If the acute LC50 or EC50 < 1 milligram/liter (mg/L). 

iv. If the estimated environmental concentration (EEC) in water is >1% of the acute 

EC50 or LC50 or if any of the following conditions exist: 

A. Studies of other organisms indicate the reproductive physiology of fish and/or 

invertebrates may be affected. 

B. Physicochemical properties indicate bioaccumulation of the pesticide. 

C. The pesticide is persistent in water (e.g., half-life in water >4 days). 

EFED has considered the following data in determining that an estuarine/marine invertebrate 

life cycle study is necessary for the ecological risk assessment, with consideration to sections 

(ii), (iv), (iv)(B), and (iv)(C) above: 

 The currently labeled use patterns of etridiazole, particularly the use on golf course 

turf, indicate that etridiazole use may occur in close proximity to estuarine/marine 

environments. 

 A Tier I analysis in the support of the Reregistration Eligibility Decision (RED)7

 for 

etridiazole determined that surface water EECs may reach 0.44 mg a.i./L. 

 Etridiazole is moderately toxic to estuarine/marine invertebrates on an acute exposure 

basis (LC50=2.5 mg a.i./L, MRID 42834603). 

 Based on these data, the peak surface water EEC = 0.18 of the acute toxicity endpoint 

for estuarine/marine invertebrates (EEC 0.44 mg a.i./L  LC50 2.5 mg a.i./L = 0.18) 

and therefore is 18 times greater than the 0.01 threshold identified in 40 CFR Part 

158.660. 

 The log octanol-water partition coefficient (log Kow) for etridiazole is 3.37, which 

indicates a potential to bioaccumulate. 

 The half-life for etridiazole in water, based on hydrolysis, ranges from 81-83 days at 

pH values of 5 to 7 and suggests that the compound may persist in water (Accession 

																																																																		 6

 CFR. 2014. Title 40 (Protection of the Environment), Chapter 1 (Environmental Protection Agency), Subchapter E (Pesticide Programs), Part 

158 (Data Requirements for Pesticides), Subpart G (Ecological Effects), §158.660 (Non-target plant protection data requirements table). 

http://www.ecfr.gov/cgi-bin/text-idx?SID=b9b5a7025cc818a6d42deb818e657b83&node=se40.24.158_1660&rgn=div8 7

 USEPA, 2000. Revised EFED Risk Assessment for the Reregistration Eligibility Decision on 5-ethoxy-e tricholoromethyl-1,2,4-thiadiazole 

(Etridiazole; Terrazole®) Environmental Protection Agency (USEPA). From Environmental Fate and Effects Division to Special Review and 

Reregistration Division. Memorandum issued: May 22, 2000. 
Page 5 of 10 

Number 00001650). Additional data are needed to evaluate biotic (aerobic and 

anaerobic aquatic) metabolism. 

EFED will evaluate any proposed label changes that may be submitted in accordance with a 

Pesticide Registration Improvement Act (PRIA) action or Registration Review and which 

may have an impact on ecological risks. However, although changes in labeled use patterns 

may result in lower exposure potential, the need still exists for estuarine/marine invertebrate 

life cycle data, particularly given etridiazole’s potential to bioaccumulate and its persistence 

in water. 

b) Guideline No. 850.4400 Aquatic Plant Toxicity Test (Using Lemna ssp.) 

The test material required for the Aquatic Plant Toxicity Test (Lemna spp.) is for an End-Use 

Product (TEP). MacDermid Agricultural Solutions, Inc. requests that the study be done on 

the TGAI using a study design that would be more suitable to the physical chemistry of the 

active. 

EFED’s response: 

EFED is limited in its ability to provide a response to this comment without clarification of 

what is meant by “a study design that would be more suitable to the physical chemistry of the 

active.” The 40 CFR Part 158.660 indicates that either a typical end-use product (TEP) or 

the technical grade active ingredient (TGAI) may be used for aquatic plant testing. However, 

EFED policy, as stated in a 1994 guidance memo8 and in the 850 test guidelines for aquatic 

plants, is that TEP is the preferred test substance for aquatic plant toxicity studies. General 

guidance from the EFED Plant Technical Team is that TEP testing should be used in these 

studies. There may be instances where aquatic plant testing with TGAI would be acceptable, 

such as cases where runoff from a treated field is expected to be the predominant route of 

exposure and solubility is not an issue. However, in cases where spray drift exposure may 

affect water bodies, solubility of the test substance is limited or the pesticide is applied 

directly to water, TEP may still need to be requested if only TGAI studies are available. The 

use of a TEP is preferred to use of a TGAI with a standard solvent. 

c) Nonguideline Honey Bee Larval Toxicity 

A guideline compliant study will be submitted. Requires protocol submission.

EFED’s response: 

EFED appreciates the registrant’s communication that it will submit data to fulfill the 

requirements for acute toxicity to honey bee (Apis mellifera) larvae and for acute oral and 

contact toxicity to young adult honey bees. We look forward to reviewing a protocol for the 

larval toxicity test prior to initiation of the experiment. 

Recently, the Agency has issued guidance9

 for assessing the potential risks of pesticides to 

bees and the data needed to support such assessments. The guidance document indicates that 

																																																																		 8

 Maciorowski, A. F. 1994. Closure on Nontarget Plant Phytotoxicity Policy Issues. Support Document #19. In: U.S. EPA. 2004. Overview of 

the Ecological Risk Assessment Process in the Office of Pesticide Programs. Office of Prevention, Pesticides, and Toxic Substances. Office of 

Pesticide Programs. Washington, D.C. January 23, 2004. 

9

 USEPA et al.. 2014. Guidance for Assessing Pesticide Risks to Bees. http://www2.epa.gov/sites/production/files/2014-

06/documents/pollinator_risk_assessment_guidance_06_19_14.pdf 
Page 6 of 10 

if exposure of bees to a pesticide is expected, a Tier I screening-level risk assessment should 

be conducted. The Tier I assessment is intended to be sufficiently conservative that 

chemicals which pass the screen can be assumed to represent a relatively low risk of adverse 

effects to bees. Tier I toxicity data that are generally needed to complete screening-level risk 

assessments include a suite of laboratory-based studies on individual bees, and consist of the 

following tests: acute contact toxicity data to adult honey bees (honey bees serving as a 

surrogate for other Apis and non-Apis bees), acute and chronic oral toxicity to adult honey 

bees, and acute and chronic oral toxicity to honey bee larvae. If risk concerns are identified 

in the screening-level assessment, the assessment may be refined using data that further 

define exposure or through additional data including Tier II semi-field or full-field toxicity 

tests conducted with whole colonies. 

Consistent with the guidance9

 that was issued shortly after the draft Problem Formulation for 

etridiazole, Tier I honey bee laboratory toxicity data are needed to conduct the screeninglevel risk assessment because exposure of bees to etridiazole residues is expected. The 

registrant has since submitted a nonguideline study testing acute and oral contact toxicity to 

the bumblebee (Bombus terrestris L.) (MRID 49460902)10. This study is in review and may 

provide useful information for risk characterization, particularly since bumblebees are 

ground-dwelling insects and are likely to be exposed to soil-incorporated etridiazole. 

Additionally, the registrant has indicated that it will submit guideline-compliant data for 

acute contact and oral toxicity for adult honey bees, and for acute larval toxicity. In support 

of the Final Work Plan for etridiazole, EFED further recommends the submission of toxicity 

data for chronic oral exposure to larval and adult honey bees, as described in the Pollinator 

Guidance. These additional recommendations are detailed in the following data rationale 

tables. 

Should the screening-level risk assessment identify risk concerns for bees, mitigation 

measures may need to be considered or the registrant may be required to conduct more 

refined studies under semi-field or full-field conditions (e.g., 850.304011 guideline studies) 

that reduce uncertainty by characterizing etridiazole’s effects at the whole-colony level. 

Guideline Number: Non-Guideline 

Study Title: Larval Honey Bee Chronic Oral Toxicity

Rationale for Requiring the Data 

This study is needed to evaluate the potential effects of technical grade active ingredient (TGAI) to honey bee larvae 

from repeat exposure. Etridiazole is used as a soil-incorporated fungicide, and is currently registered for use on 

tobacco, tomato, turf (golf-course tees, greens and fairways), on ornamental plants, and commercial nurseries. These 

use patterns may result in exposure to blooming plants and could result in residues in pollen and nectar (which could 

then be transported to the hive by adult forager bees). Additionally, etridiazole is moderately persistent, at least 

locally systemic in plants, and can be absorbed through the foliage and roots. Therefore, in addition to direct 

contamination of pollen and/or nectar through foliar applications, etridiazole residues may be translocated to pollen 

and nectar from root uptake in plants grown where etridiazole has been applied. 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. Therefore, exposure at all bee life stages would be expected. 

																																																																		 10 Verge, E. 2012. Terrazole 48EC (UBI 8142.00): Acute Oral and Contact Toxicity to the Bumblebee, Bombus terrestris L. (Hymenoptera, 

Apidae) under Laboratory Conditions (Multi Dose Test). Submitted September 26, 2014. MRID 49460902. 11 USEPA. 2012. Ecological Effects Test Guidelines OCSPP 850.3040: Field Testing for Pollinators. Office of Chemical Safety and Pollution 

Prevention (7101). EPA 712-C-017 January 2012. 
Page 7 of 10 

The Agency finalized its guidance12 for assessing risks to bees and now requires this study for all use sites where 

potential exposure to pollinators may occur. Although EPA has not developed a guideline for this study, the 21-day 

larval toxicity study currently under development by OECD13 provides a draft guidance protocol for potentially 

assessing both the acute and chronic toxicity to developing brood (larvae and pupae) from repeat exposure to 

pesticides. A protocol should be submitted to the Agency for review and approval prior to study initiation. 

Practical Utility of the Data 

How will the data be used and how could the data impact the Agency’s future decision-making? 

The 21-day larval toxicity study provides data on the effects of technical grade active ingredient (TGAI) on developing 

bees from acute (short-term) and chronic (longer term) exposure and will be used for estimating risk to individual 

(solitary) bees as well as bee colonies (social bees). 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. 

These data are needed for risk assessments written in support of Registration Review as well as for future 

endangered species assessments. These data would allow the Agency to better characterize the potential for risk to 

insects (including beneficial pollinators) from the use of etridiazole. These data may help the Agency determine 

whether any mitigations are needed. If the Registration Review and any future endangered species risk assessments 

are performed without these data, the Agency would have to assume that etridiazole "may affect" insects, including 

bees and beneficial pollinators, directly (and endangered species from other taxa indirectly), and uses of etridiazole 

might need to be restricted in areas where pollinators could be exposed. 

Guideline Number: Non-Guideline 

Study Title: Adult Honey Bee Chronic Oral Toxicity

Rationale for Requiring the Data 

This 10-day study is needed to evaluate the potential effects of technical grade active ingredient (TGAI) on young 

adult honey bees from repeat exposure. Etridiazole is used as a soil-incorporated fungicide, and is currently 

registered for use on tobacco, tomato, turf (golf-course tees, greens and fairways), on ornamental plants, and 

commercial nurseries. These use patterns may result in exposure to blooming plants and could result in residues in 

pollen and nectar (which could then be transported to the hive by adult forager bees). Additionally, etridiazole is 

moderately persistent, at least locally systemic in plants, and can be absorbed through the foliage and roots. 

Therefore, in addition to direct contamination of pollen and/or nectar through foliar applications, etridiazole residues 

may be translocated to pollen and nectar from root uptake in plants grown where etridiazole has been applied. 

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. Therefore, exposure at all bee life stages would be expected. 

The Agency has finalized its guidance14 for assessing risks to bees and now requires this study for all use sites 

where potential exposure to pollinators may occur. Although EPA has not developed a guideline for this study and 

OECD has yet to finalize test guidance for chronic studies, efforts are currently underway to develop standardized 

guidelines for assessing effects from chronic (10-day) exposures to adult bees in the laboratory. A protocol should 

be submitted to the Agency for review and approval prior to study initiation. 

Practical Utility of the Data 

How will the data be used and how could the data impact the Agency’s future decision-making? 

The 10-day toxicity study with young adult bees provides data that will be used in estimating chronic risk to 

individual adult bees. 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. 

These data are needed for risk assessments written in support of Registration Review as well as for future 

endangered species assessments. These data would allow the Agency better characterize the potential for risk to 

insects (including beneficial pollinators) from the use of etridiazole. These data may help the Agency determine 

whether any mitigations are needed. If the Registration Review and any future endangered species risk assessments 

																																																																		 12 Ibid USEPA et al. 2014. 13 OECD. 2013. OECD Draft Guidance Document Honey Bee (Apis mellifera) Larval Toxicity Test, Repeated Exposure. Revision of June 2013 

draft GD, 25 November 2013. http://www.oecd.org/env/ehs/testing/Draft_GD_honeybees_rep_exp_for_2nd_CR_25_November_2013.pdf		 14 Ibid USEPA et al. 2014. 
Page 8 of 10 

are performed without these data, the Agency would have to assume that etridiazole "may affect" insects, including 

bees and beneficial pollinators, directly (and endangered species from other taxa indirectly), and uses of etridiazole 

might need to be restricted in areas where pollinators could be exposed.

3. Physician’s Committee for Responsible Medicine (PCRM)

a) Guideline No. 850.2100 Acute Avian Oral Toxicity 

We recommend that OECD Test Guideline 223, Avian Acute Oral Toxicity Test, be used as 

the protocol instead of EPA Guideline 850.2100 in the interest of reducing the numbers of 

animals used by up to 61%. We also refer the registrant to the “Guidance for Classifying 

Studies Conducted Using the OECD Test Guideline 223 (TG223) (Acute Avian Oral 

Sequential Dose Study)” available on the Agency’s website.

EFED’s response: 

EFED encourages careful consideration of the limitations and appropriateness of the 

Organization for Economic Cooperation and Development (OECD) Test Guideline 22315 for 

a given test chemical and species. For example, it is important to document that background 

mortality for the test species is less than 1% in a given laboratory, and that the species has a 

low propensity to regurgitate. Specific recommendations are outlined in the document 

referenced by PCRM, “Guidance for Classifying Studies Conducted Using the OECD Test 

Guideline 223 (TG223) (Acute Avian Oral Sequential Dose Study)” (November 9, 2011). 

This document is publicly available at the following web address: 

http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/terrestrial_biolog

y_tech_team/review_avian_acute_oral_oecd_tg223.pdf 

To address the potential for regurgitation in test birds, EFED has provided “Guidance for 

Use When Regurgitation is Observed in Avian Acute Toxicity Studies with Passerine Species” 

(April 9, 2012). Note that the OECD 223 test design is not appropriate for use when 

regurgitation occurs. The guidance is publicly available at 

http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/terrestrial_biolog

y_tech_team/rr_regurg_acute_passerine.pdf 

More recently, EFED publicly shared its internal guidance for reviewers: “Guidance for 

Reviewing OCSPP 850.2100 Avian Oral Toxicity Studies Conducted with Passerine Birds”16

(August 20, 2014). This document is specific to studies conducted using OCSPP 850.2100 

and does not address studies which may be conducted using OECD Test Guideline 223. 

b) Guideline No. 850.1075 Fish Acute Toxicity Test (3-Carb-T and 3-DCMT 

degradates) (freshwater and estuarine/marine) 

We refer the Agency to the following study to be taken into consideration for the fish acute 

																																																																		 15 OECD 2009. OECD Guideline for the Testing of Chemicals. Avian Acute Oral Toxicity Test. OECD/OCDE 223 Adopted: 22 July 2010. 

http://www.oecd-ilibrary.org/environment/test-no-223-avian-acute-oral-toxicity-test_9789264090897-en 16 USEPA. 2014. Guidance for Reviewing OCSPP 850.2100 Avian Oral Toxicity Studies Conducted with Passerine Birds. 

http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/terrestrial_biology_tech_team/passerine_ocspp850_2100_avian_oral_

tox.pdf

			
Page 9 of 10 

toxicity test. The study is available in the California Department of Pesticide Regulation 

records for Terrazole.2 

... 

2

 http://apps.cdpr.ca.gov/ereglib/, chemical code 580. 

EFED’s response: 

In response to the Preliminary Work Plan, EFED notes that the registrant has submitted 

existing study reports on the acute toxicity of the etridiazole degradate 3-Carb-T (also 

referred to as T-02) to freshwater fish17 and invertebrates18; these studies are in review 

(MRIDs 49460903 and -04). The registrant indicated that it will submit a guideline 

compliant study for acute toxicity of the degradate 3-DCMT to estuarine/marine fish.19

EFED was unable to obtain any study document using the link provided by PCRM. As with 

other data requirements, a registrant may submit non-guideline data for consideration by the 

Agency, along with a rationale explaining how the submitted data may address a given data 

requirement. 

c) Guideline No. 850.1075 Fish Acute Toxicity Test (3-Carb-T and 3-DCMT 

degradates) (freshwater and estuarine/marine) (continued)

If these data are not sufficient then we recommend the registrant consider an alternative 

strategy that can supplement otherwise unacceptable fish toxicity data or provide 

information on the concentrations likely to cause acute fish toxicity. Such a strategy includes 

the newly-adopted Fish Embyrotoxicity Test guideline (FET) (OECD TG 236), an acute 

threshold estimation approach, and QSAR or read-across methods. Together these methods 

may in some cases provide enough information to set safe exposure levels without conducting 

additional live fish testing. 

EFED’s response: 

EFED recognizes the importance of reducing animal testing and will consider multiple lines 

of evidence in its risk assessment. The methods identified by PCRM may be useful for risk 

characterization. However, there are significant uncertainties associated with each of the 

methods identified by the registrant and these uncertainties may limit the utility of these 

studies for quantitatively assessing risk from the use of etridiazole. The Agency continues to 

evaluate the Fish Embryo Toxicity (FET)20 method and its potential utility for risk 

assessment, but the FET method has not been identified as a suitable substitute for testing the 

acute toxicity to fish using OCSPP 850.107521 at this time. Similarly, while an acute 

threshold approach22 using alga or invertebrates may seem appealing, the biological and 

																																																																		 17 Cafarella, M.A. 2000. T-02 acute toxicity to rainbow trout (Onchorhynchus mykiss) under static conditions. Submitted September 3, 2014. 

MRID 49460904. 

18 Cafarella, M.A. 2000. T-02 acute toxicity to daphnids (Daphnia magna) under static conditions. Submitted September 3, 2014. MRID 

49460903. 

19 MacDermid Agricultural Solutions, Inc. 2014. Letter to the Office of Pesticide Programs Docket (EPA-HQ-OPP-2014-0414). 20 OECD. 2013. Test Guideline 236: Fish Embryo Acute Toxicity Test. OECD Guidelines for the 

Testing of Chemicals. Available at: http://www.oecd-ilibrary.org/environment/test-no-236-fishembryo-acute-toxicity-fet-test_9789264203709-en. 

Accessed August 25, 2014. 

21 USEPA. 1995. Ecological Effects Test Guidelines OCSPP 850.1075. Fish Acute Toxicity Test, Freshwater and Marine. Office of Chemical 

Safety and Pollution Prevention formerly the Office of Prevention, Pesticides and Toxic Substances (7101). EPA 712-C-96-118. April 1996. 

http://www.epa.gov/ocspp/pubs/frs/publications/OPPTS_Harmonized/850_Ecological_Effects_Test_Guidelines/Drafts/850-1075.pdf 22 OECD. 2010. Series on Testing and Assessment No. 126. Short Guidance on the Threshold 
Page 10 of 10 

quantitative relevance of effects seen in these taxonomic groups is difficult to extrapolate to 

fish, and effects from such studies would do little to inform risk characterization for fish and 

aquatic amphibians. Finally, the accuracy of Quantitative Structure-Activity Relationships 

(QSAR) and other inference methods23,24 is dependent on the quantity and quality of 

underlying data on chemicals with similar structures and mechanisms of action. It is 

uncertain to what extent appropriate data are available for molecules that are chemically 

similar to etridiazole’s environmental degradates to support a robust QSAR analysis. 

However, if the registrant can provide evidence consistent with that identified in the North 

American Free Trade Agree (NAFTA) guidance25 on the use of QSARs that etradiazole 

degradates fall within the range of applicability for these models, EPA will consider this 

evidence in determining whether additional testing is needed with the degradates. 

																																																																		 Approach for Acute Fish Toxicity. Available at 

http://ntp.niehs.nih.gov/iccvam/suppdocs/feddocs/oecd/oecd-gd126.pdf. Accessed August 25, 2014. 23 OECD. 2010. (Q)SAR Application Toolbox Version 1.1: Strategies for grouping chemicals for 

data gap filling for acute aquatic toxicity endpoints. Available online at 

http://www.oecd.org/dataoecd/4/47/45133663.pdf. 24 North American Free Trade Association (NAFTA). 2012. Quantitative Structure Activity Relationship [(Q)SAR] Guidance Document. 

Technical Working Group on Pesticides. Available online at http://www.epa.gov/oppfead1/international/naftatwg/guidance/qsar-guidance.pdf. 25 Ibid NAFTA. 2012.