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OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON D.C., 20460 

 

 PC Code: 018986 

 DP Barcode: D409544 

 Date: February 10, 2015 

MEMORANDUM 

SUBJECT: Environmental Fate and Ecological Risk Assessment for Use of the New 

Herbicide Bicyclopyrone (NOA449280) 

TO: Erick Kraft, Risk Manager Reviewer

 Shaja Joyner, Product Manager

 Rachel Holloman, Branch Chief

 Fungicide and Herbicide Branch

Registration Division (7505P)

 

FROM: Andrew Sayer, Ph.D., Biologist 

 Cheryl Sutton, Ph.D., Environmental Scientist 

 Environmental Risk Branch IV 

 Environmental Fate and Effects Division (7507P)

REVIEWED Thomas Steeger, Ph.D., Senior Science Advisor 

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

 Environmental Risk Branch IV 

 Environmental Fate and Effects Division (7507P) 

APPROVED 

BY: Jean Holmes, DVM, Branch Chief 

 Environmental Risk Branch IV 

 Environmental Fate and Effects Division (7507P)

The Environmental Fate and Effects Division (EFED) has completed a review of the new 

herbicide bicyclopyrone (PC Code 018986) and its proposed use on corn as a pre-emergent or 

early post-emergent herbicide via ground spray application. The review assessed two formulated 

end-use products, as a soluble concentrate (SC, in SYN-A16003; 18.1% a.i.) and a mixed 

formulation capsule suspension and suspension concentrate (ZC; in SYN-A19707; 0.65% a.i.) 

herbicide. The mixed formulation product, which is proposed as a restricted use (RU) pesticide, 

also contains atrazine (PC Code 080803), mesotrione (PC Code 122990), and S-metolachlor (PC 

Code 108800). This evaluation is limited to the exposure associated with bicyclopyrone 
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specifically and not the other compounds; however, the likelihood of adverse effects from 

exposure to the formulated product(s) is assessed, where data are sufficient to permit such 

analyses, based on the content of bicyclopyrone in the relevant formulations. For environmental 

exposure, only the parent compound alone is considered a residue of concern. 

Based on peak estimated environmental concentrations (EECs) and the most sensitive 

ecotoxicity data across multiple taxa, bicyclopyrone exposure at the maximum proposed 

application rates may result in risk to federally listed threatened and endangered (hereafter 

referred to as “listed”) species of terrestrial and semi-aquatic dicotyledonous (dicot) plants. Risk 

estimates also exceed the levels of concern (LOC) for listed and non-listed vascular aquatic 

plants and the chronic risk LOC for mammals. 

Data Gaps/Uncertainties 

Environmental Fate/Exposure 

There are no environmental fate data gaps for bicyclopyrone; however, there is some uncertainty 

introduced by a supplemental non-guideline aerobic aquatic metabolism study in which the test 

soil was irradiated during the incubation (MRID 47842075). Because of the multiple issues 

associated with the study, it is classified as “reliable with restrictions.” 

Additionally, the registrant has sought to show that parent compound transported below the soil 

surface may be wicked upward through evaporative transport flux in the soil and subsequently 

photodegraded on the surface soil, resulting in more rapid degradation than would occur in soil 

through metabolism alone (MRIDs 47842030, 47842170). However, in prospective groundwater 

studies following parent bicyclopyrone application, the soil transformation product SYN503780 

was detected in wells at sampling intervals up to 3 years after application. 

The labels specify that bicyclopyrone is generally to be applied once annually; however, a split 

application for pre-emergent and early post-emergent is allowed, provided the maximum 

recommended application/year of 0.04 lb a.i./A (50 g/ha) is not exceeded. Aquatic exposure in 

this assessment is based on the single pre-emergent application. If a split application is used, the 

acute aquatic exposure in the environment may be less than that quantified in this assessment. 

Terrestrial exposure in this assessment is based on a single application. Also, if applied as a preemergent, bicyclopyrone will be applied to the soil surface rather than on growing plants. Thus, 

actual terrestrial exposure in the environment may be less than that estimated quantitatively in 

this assessment. 

Ecological Effects 

No data have been submitted for chronic toxicity to estuarine/marine fish and invertebrates. 

Therefore, a mysid chronic toxicity test (OCSPP 850.1350) and estuarine/marine fish early-life 

stage test (OCSPP 850.1400) are classified as data gaps. However, acute-to-chronic ratios 

(ACRs) have been calculated based on freshwater toxicity data to estimate chronic toxicity 

endponts for estuarine/marine fish and invertebrates. 
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The submitted acute oral toxicity study to a passerine species (OCSPP 850.2100; MRID 478420-

78) was classified as supplemental because regurgitation and mortality across the multiple 

concentrations tested. Furthermore, the study suggests that passerines may be more sensitive to 

either the mallard duck or bobwhite quail and thus would be important in the characterization for 

avian taxa. EFED has developed guidance on the testing of passerines where regurgitation has 

been an issue1; this guidance indicates that a dietary study should be conducted in the event 

regurgitation cannot be prevented. 

Although data indicate bicyclopyrone is practically non-toxic to young adult bees on both an 

acute contact and oral exposure basis, there is uncertainty regarding the potential acute and 

chronic effects of the compound on honey bee larval development and survival as well as 

potential for chronic effects of adult bees. Since bicyclopyrone is a systemic herbicide, residues 

may be present in pollen and/or nectar and represent a route of exposure for bees through both 

contact and ingestion. Therefore, additional data on pollinators is needed to fully characterize 

the risk associated with bicyclopyrone use to all developmental stages of honey bees, as 

sensitivity may vary according to life-stage and length of exposure (adult vs. larval and acute vs. 

chronic, respectively). As described in the guidance for assessing risks to bees2,3, depending on 

the outcome of the screening-level risk assessment, additional studies of bees at the colony level 

under semi- and full-field conditions may also be recommended. 

Label Recommendations 

As noted in the Label Review Manual4, since the product is intended for outdoor use, the 

following statement should appear in the Environmental Hazards Section: 

 

“For terrestrial uses: Do not apply directly to water, or to areas where surface water is present 

or to intertidal areas below the mean high water mark. Do not contaminate water when 

disposing of equipment washwater or rinsate”. 

 “Bicyclopryrone is known to leach through soil into groundwater under certain conditions as a 

result of label use. This chemical may leach into groundwater if used in areas where soils are 

permeable, particularly where the water table is shallow.” 

Label language pertaining to Environmental Hazard Statements differs between labels for the 

two end-use products, with one prohibiting discharge of effluent containing bicyclopyrone 

without a National Pollutant Discharge Elimination System (NPDES) permit, and the other 

prohibiting direct application to water or contamination of washwater or rinsate. While Ground 

 

1

 USEPA. 2012. Guidance for Use When Regurgitation is Observed in Avian Acute Toxicity Studies with Passerine Species. Memorandum 

from Donald J. Brady. 

http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/terrestrial_biology_tech_team/rr_regurg_acute_passerine.pdf 2

USEPA. 2014. Guidance for Assessing Pesticide Risks to Bees. Office of Pesticide Programs. United States Environmental Protection Agency. 

Available at 

http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/terrestrial_biology_tech_team/GuidanceAssessingPesticideRisk2Bees.

pdf 3

http://www2.epa.gov/sites/production/files/2014-06/documents/pollinator_risk_assessment_guidance_06_19_14.pdf 4

 USEPA. 2012. Lavel Review Manual, Chapter 8: Environmental Hazards. http://www2.epa.gov/sites/production/files/documents/chap08_2.pdf 
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Water Advisories are already on the proposed label for the product SYN-A19707, which also 

contains the active ingredients atrazine and s-metolachlor, it is not on the label for the product 

SYN-A16003, although bicyclopyrone chemical properties are similar to other chemicals which 

have been found in groundwater, and bicyclopyrone and one of its degradates was detected in 

submitted Prospective Groundwater Monitoring studies. 

With respect to NPDES statements, the Label Review Manual recommends the following 

statement: 

“Do not discharge effluent containing this product into lakes, streams, ponds, estuaries, oceans, 

or other waters unless in accordance with the requirements of a National Pollutant Discharge 

Elimination System (NPDES) permit and the permitting authority has been notified in writing 

prior to discharge. Do not discharge effluent containing this product to sewer systems without 

previously notifying the local sewage treatment plant authority. For guidance contact your State 

Water Board or Regional Office of the EPA”. 

Given the expected high mobility of the parent compound, the label should also state: 

“This product has a high potential for reaching surface water via runoff for several months or 

more after application A level, well-maintained vegetative buffer strip between areas to which 

this product is applied and surface water features such as ponds, streams, and springs will 

reduce the potential loading of bicyclopyrone from runoff water and sediment. Runoff of this 

product will be reduced by avoiding applications when rainfall or irrigation is expected to occur 

within 48 hours.” 
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Environmental Fate and Ecological Risk Assessment for Use of the 

new Herbicide Bicyclopyrone (NOA449280) 

O CF3

N

OH O

O

OMe

Bicyclopyrone

CAS 352010-68-5 PC Code 018986 

10 February 2015 

Prepared by

Andrew Sayer, Ph.D., Biologist

Cheryl Sutton, Ph.D., Environmental Scientist

U.S. Environmental Protection Agency

Office of Pesticide Programs 

Environmental Fate and Effects Division (EFED) 

Environmental Risk Branch IV 

1200 Pennsylvania Ave., NW 

Mail Code 7507P 

Washington, DC 20460 Reviewed by

Thomas Steeger, Ph.D., Senior Science Advisor

Jim Carleton, Ph.D., Senior Fate Scientist

Jean Holmes, D.V.M., Branch Chief
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Table of Contents 

1. Executive Summary ........................................................................................................................................... 9

2. Problem Formulation ...................................................................................................................................... 10

2.1. Nature of Chemical Stressor ................................................................................................................... 10

2.2. Stressor Source and Distribution ............................................................................................................ 10

2.3. Receptors................................................................................................................................................... 11

2.4. Assessment Endpoints .............................................................................................................................. 11

2.5. Conceptual Model .................................................................................................................................... 12

2.5.1. Risk Hypothesis ............................................................................................................................... 12

2.5.2. Conceptual Model Pathways and Effects ...................................................................................... 12

2.6. Analysis Plan ............................................................................................................................................ 14

2.6.1. Conclusions from Previous Risk Assessments .............................................................................. 14

2.6.2. Identification of Data Gaps and Uncertainties ............................................................................. 14

2.6.3. Measures of Exposure ..................................................................................................................... 15

2.6.4. Measures of Effect ........................................................................................................................... 16

2.6.5. Integration of Exposure and Effects .............................................................................................. 17

3. Analysis ............................................................................................................................................................. 18

3.1. Use Characterization ............................................................................................................................... 18

3.2. Exposure Characterization ...................................................................................................................... 18

3.2.1. Environmental Fate and Transport ............................................................................................... 18

3.2.2. Aquatic Exposure ............................................................................................................................ 26

3.2.3. Terrestrial Exposure ....................................................................................................................... 29

3.3. Ecological Effects Characterization ........................................................................................................ 31

3.3.1. Ecotoxicity Data ............................................................................................................................... 31

3.3.1. Terrestrial Organism and Mammalian Chronic Endpoints ........................................................ 42

3.3.2. Terrestrial Plants ............................................................................................................................. 44

3.3.3. Incident Reports .............................................................................................................................. 46

4. Risk Characterization ...................................................................................................................................... 46

4.1. Risk Estimation ........................................................................................................................................ 46

4.1.1. Aquatic Organisms .......................................................................................................................... 46

4.1.2. Terrestrial Organisms ..................................................................................................................... 48

4.2. Risk Description and Conclusions .......................................................................................................... 52

4.2.1. Aquatic Organisms .......................................................................................................................... 52

4.2.2. Terrestrial Organisms ..................................................................................................................... 52

4.2.3. Conclusions ...................................................................................................................................... 53

5. Federally Threatened and Endangered (Listed) Species of Concern .......................................................... 54

5.1. Action Area ............................................................................................................................................... 54

5.2. Taxonomic Groups Potentially at Risk .................................................................................................. 55

6. References ......................................................................................................................................................... 58

List of Tables 

Table 2.1. List of the various models and the related taxa for which the models will be used to assess risk. .... 13

Table 3.1. Summary of use information for the bicyclopyrone proposed use on corn. ....................................... 18

Table 3.2. Leaching Depths and Concentrations in U.S. Terrestrial Field Dissipation Studies ......................... 20

Table 3.3. Chemical properties and environmental fate parameters of bicyclopyrone. ...................................... 21

Table 3.4. Input values for the SWCC model for bicyclopyrone1.......................................................................... 26

Table 3.5. SWCC scenarios and inputs for bicyclopyrone modeling .................................................................... 27

Table 3.6. Input Values for the SCI-GROW model for bicyclopyrone. ................................................................ 27

Table 3.7. Input values for the PRZM-GW model for bicyclopyrone. .................................................................. 28

Table 3.8. Estimated environmental concentrations for bicyclopyrone use on corn. .......................................... 29

Table 3.9. PRZM-GW and SCI-GROW groundwater EECs for bicyclopyrone use on corn. ............................ 29
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Table 3.10. Terrestrial EECs as food residues for animals exposed to bicyclopyrone as a result of the 

proposed pre-emergent use. ...................................................................................................................................... 30

Table 3.11. EECs for non-target terrestrial and semi-aquatic plants based on proposed use of bicyclopyrone 

(TerrPlant). ................................................................................................................................................................ 31

Table 3.12. Acute toxicity endpoints used in risk estimation and characterization for freshwater organisms 

exposed to bicyclopyrone. ......................................................................................................................................... 34

Table 3.13. Acute toxicity endpoints used in risk estimation and characterization for estuarine/marine 

organisms exposed to bicyclopyrone. ....................................................................................................................... 34

Table 3.14. Toxicity endpoints used in risk estimation and characterization for aquatic plants and algae 

exposed to bicyclopyrone. ......................................................................................................................................... 35

Table 3.15. Chronic toxicity endpoints used in risk estimation and characterization for fish and aquatic 

invertebrates exposed to bicyclopyrone. .................................................................................................................. 37

Table 3.16. Acute toxicity endpoints used in risk estimation and characterization for birds and mammals 

exposed to bicyclopyrone. ......................................................................................................................................... 40

Table 3.17. Acute toxicity endpoints used in risk estimation and characterization for terrestrial invertebrates 

exposed to bicyclopyrone. ......................................................................................................................................... 40

Table 3.18. Chronic toxicity endpoints used in risk estimation and characterization for terrestrial animals 

exposed to bicyclopyrone. ......................................................................................................................................... 43

Table 3.19. Toxicity endpoints used in risk estimation and characterization for terrestrial and semi-aquatic 

plants exposed to bicyclopyrone. .............................................................................................................................. 44

Table 3.20: Most sensitive 21-day seedling emergence endpoints for plant species exposed to bicyclopyrone . 45

Table 3.21: Most sensitive 21-day vegetative vigor endpoints for plant species exposed to bicyclopyrone ....... 46

Table 4.1. Acute and chronic RQ values for freshwater fish and invertebrates exposed to bicyclopyrone TGAI 

in surface water. ......................................................................................................................................................... 47

Table 4.2. Acute and chronic RQ values for freshwater fish and invertebrates exposed to bicyclopyrone TEP 

(A16003E) in surface water. ...................................................................................................................................... 47

Table 4.3. Acute and chronic RQ values for estuarine/marine fish and invertebrates exposed to bicyclopyrone 

TGAI in surface water. ............................................................................................................................................. 47

Table 4.4. RQ values for listed and non-listed vascular and nonvascular aquatic plants exposed to 

bicyclopyrone TGAI in surface water as a result of spray drift only, based on maximum application rates for 

corn. ............................................................................................................................................................................ 48

Table 4.5. RQ values for listed and non-listed vascular aquatic plants exposed to bicyclopyrone TEP 

(A15749AD) in surface water as a result of spray drift only, based on maximum application rates for corn. . 48

Table 4.6. RQ values for listed and non-listed nonvascular aquatic plants exposed to bicyclopyrone TEP 

(A16003E) in surface water as a result of spray drift only, based on maximum application rates for corn...... 48

Table 4.7. Acutea avian, sub-acute dietary, and chronic,b dietary-based RQ values for TGAI bicyclopyrone. . 49

Table 4.8. Acute mammalian dose-based RQ values for proposed pre-emergent use of bicyclopyrone on 

corn.1,2 ......................................................................................................................................................................... 49

Table 4.9. Chronic mammalian dose-based RQ values for proposed pre-emergent use of bicyclopyrone on 

corn.1

 ........................................................................................................................................................................... 50

Table 4.10. RQ values for non-listed species1 of non-target terrestrial and semi-aquatic plants based on 

bicyclopyrone on corn (TerrPlant). .......................................................................................................................... 50

Table 4.11. RQ values for listed species1 of non-target terrestrial and semi-aquatic plants based on 

bicyclopyrone on corn (TerrPlant). .......................................................................................................................... 50

Table 4.12. Seedling Emergence RQ values for listed and non-listed species1 of non-target plants based on 

bicyclopyrone on corn using groundwater-derived irrigation water. ................................................................... 51

Table 4.13. Vegetative vigor RQ values for listed and non-listed species1 of non-target plants based on 

bicyclopyrone on corn using groundwater-derived irrigation water. ................................................................... 51

Table 4.14. PossibleEffects Distance for Nontarget Terrestrial Plants Exposed to Bicyclopyrone through 

Spray Drift Only Based on the Most Sensitive Crop Species in Submitted Toxicity Studies. ............................. 51

Table 5.1. Potential effects to federally listed avian taxa associated with the proposed used of TGAI 

bicyclopyrone. ............................................................................................................................................................ 57

Appendices 

Appendix A. Proposed New Uses, Bicyclopyrone .................................................................................................. 67
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Appendix B. Bicyclopyrone and its Environmental Transformation Products .................................................. 68

Appendix C. SWCC Results .................................................................................................................................... 76

Appendix D. Groundwater Modeling Results ........................................................................................................ 81

Appendix E. Example STIR (v. 1.0) input and output data .................................................................................. 83

Appendix F. Ecotoxicity data gaps and uncertainties ........................................................................................... 84

Appendix G. Example T-REX (v. 1.5.2) input and output data ........................................................................... 86

Appendix H. Example TerrPlant (v. 1.2.2) input and output data ....................................................................... 88
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1. Executive Summary 

Bicyclopyrone is characterized as a selective, systemic herbicide belonging to the 

hydroxyphenylpyruvate dioxygenase (HPPD)-inhibitor class, and is purportedly within the 

subclass of the tri-ketone chemistry (although only two ketone groups are evident). It is intended 

as a pre-emergence to early post-emergence herbicide and is applied using standard ground 

spraying equipment. Bicyclopyrone is generally applied once annually; however, a split 

application for pre-emergent and early post-emergent is allowed, provided the maximum rate of 

0.04 lb a.i./A (50g/ha) per year, with a minimum 14-day application interval, is not exceeded. 

Bicyclopyrone is a relatively soluble, nonvolatile compound that is stable to hydrolysis and is 

expected to be very highly mobile in soil. Bicyclopyrone photodegrades on surface soil, with 

half-lives ranging from 4 to 13 days. In laboratory studies conducted in darkness, it is slightly 

persistent to persistent in aerobic soil, metabolizing to multiple organic transformation products 

and carbon dioxide. It is stable in anaerobic soil and anaerobic aquatic systems, and only 

degrades very slowly in aerobic aquatic systems, with half-lives of 393-681 days. Bicyclopyrone 

photodegrades slowly in water, with half-lives of 11 to 75 days. Based on its octanol-water 

partition coefficient (log Kow -1.2 at pH 7), bicyclopyrone is not expected to bioaccumulate in 

aquatic and terrestrial organisms. 

Bicyclopyrone may move to groundwater via leaching, and may move to surface water bodies 

via spray drift and runoff of dissolved or sorbed residues. In aerobic soil metabolism studies, 

two of the major transformation products (including SYN503780) were found to be nonpersistent in aerobic soil, with half-lives of <1 -7.1 days. Laboratory metabolism and field 

studies also showed in general that persistence in the environment was not an expected issue for 

these transformation products. However, in prospective groundwater monitoring studies 

following bicyclopyrone application the transformation product SYN503780 was detected in 

wells at up to 3 years after application. 

 

Bicyclopyrone is classified as slightly to practically non-toxic to freshwater and estuarine/marine 

fish (and to aquatic-phase amphibians for which freshwater fish serve as surrogates) as well as to 

freshwater invertebrates, but is moderately toxic to estuarine/marine invertebrates on an acute 

exposure basis. An end-use product (A16003E) of bicyclopyrone is classified as slightly toxic to 

freshwater fish and invertebrates (although reported toxicity endpoints in studies using A1600E 

were greater than the highest concentration tested and not tested at concentrations as high as the 

technical grade active ingredient [TGAI] bicyclopyrone). Bicyclopyrone is slightly to 

moderately toxic to birds on an acute oral exposure basis and is practically non-toxic to birds 

(and to terrestrial-phase amphibians and reptiles for which birds serve as surrogates) on a 

subacute dietary exposure basis. The compound is classified as practically non-toxic to 

mammals on an acute oral exposure basis and it is practically non-toxic to and to young adult 

honey bees (Apis mellifera) on both an acute contact and oral exposure basis. No statistically 

significant effects were observed in either the freshwater fish early life stage toxicity test or the 

freshwater invertebrate full life cycle test after chronic exposure to bicyclopyrone. No chronic 

estuarine/marine fish or invertebrate studies were submitted and therefore acute-to-chronic ratios 

(ACRs) were used to estimate chronic toxicity endpoints for estuarine/marine animals. 

Mammalian chronic effects included decreased growth. Chronic effects in birds included 
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decreased hatchling growth in both bobwhite quail (Colinus virginianus) and mallard ducks 

(Anas platyrhynchos). 

Toxicity to aquatic vascular and non-vascular plants was observed upon exposure to 

bicyclopyrone. Additionally, exposure to the formulated product A15749AD resulted in 

decreased growth of vascular aquatic plants while bicyclopyrone metabolites CSAA589691 and 

CSCC163768 had no effect. While toxic effects were observed in nonvascular green algae and 

freshwater and marine diatoms, no toxic effects were observed in blue-green algae following 

bicyclopyrone exposure. The end-use product A16003E, also tested using green algae, resulted 

in a more sensitive toxicity endpoint than the TGAI. 

Bicyclopyrone typical end-use product (TEP) A15749F (containing 150 g a.i./L bicyclopyrone) 

exhibited effects (decreased growth) with the terrestrial monocotyledonous (monocot) ryegrass 

and dicotyledonous (dicot) cabbage plants being the most sensitive species in seedling 

emergence studies, and the monocot onion and dicot sunflower being the most sensitive plants in 

the vegetative vigor studies. 

Bicyclopyrone exposure at the labeled application rates may result in risk to federally listed 

threatened and endangered (hereafter referred to as “listed”) species of terrestrial and semiaquatic dicots. Risk to listed dicot plants exceeds the Agency’s level of concern (LOC) for preemergent use (i.e., on cabbage and sunflower). The likelihood of acute mortality in fish, 

invertebrates, mollusks, aquatic-phase amphibians, birds, reptiles, terrestrial-phase amphibians, 

and mammals is considered low as RQ values do not exceed the Agency’s acute risk LOC. 

Conversely, dose-based RQ values exceed the chronic risk LOC for mammals. Since 

bicyclopyrone is practically non-toxic to adult bees on an acute exposure basis, no RQ values are 

calculated; however, there is uncertainty regarding the potential for adverse effects on honey bee 

adults from chronic exposure and to honey bee larvae from either acute or chronic exposure. 

2. Problem Formulation 

2.1. Nature of Chemical Stressor 

Bicyclopyrone [4-hydroxy-3-[[2-[(2-methoxyethoxy) methyl]-6-(trifluoromethyl)-3-pyridinyl] 

carbonyl]bicyclo[3.2.1]oct-3-en-2-one; CAS# 352010-68-5) is a selective, systemic herbicide of 

the HPPD-inhibitor class, and is in the subclass of the tri-ketone chemistry. Bicyclopyrone 

inhibits the enzyme hydroxyphenylpyruvate dioxygenase (HPPD) in the chlorophyll biosynthesis 

pathway. The mode of action of bicyclopyrone is shared with multiple other registered active 

ingredients, such as mesotrione, isoxaflutole, topramezone, tembotrione, pyrasulfatole. 

Bicyclopyrone is intended to control broad leaf weeds and annual grasses in corn in the U.S and 

is also undergoing registration for use in Canada on corn and in Australia for use on sugarcane. 

2.2. Stressor Source and Distribution 

Bicyclopyrone is contained in two formulated end-use products, as a soluble concentrate (SC, in 

SYN-A16003; 18.1% a.i.) or mixed formulation capsule suspension and suspension concentrate 

(ZC; in SYN-A19707; 0.65% a.i.) herbicide. Bicyclopyrone is proposed for use in corn as a pre-
-Page 11 of 88- 

emergent or early post-emergent herbicide via ground spray application. The mixed formulation 

product, which is proposed as a restricted use (RU) pesticide, also contains atrazine, mesotrione, 

and S-metolachlor. This evaluation is limited to the exposure associated with bicyclopyrone 

specifically and not the other compounds; however, risk based on exposure to the formulated 

product(s) is assessed, where data are sufficient to permit analysis, based on the content of 

bicyclopyrone in the relevant formulations. 

For ecological exposure, only the parent compound is considered a residue of concern. Major 

environmental transformation products of a compound may be of exposure concern. Available 

environmental fate data indicate that the five major transformation products CSCC163768 

(SYN504810), CSAA589691 (NOA412101), CSCD642512 (SYN545859), CSCD656832 

(SYN545680) and SYN503780 (CSAA794148) may be present in the environment following 

use of bicyclopyrone. These degradates of exposure concern were further examined to determine 

which of them might be a factor in risk (rather than exposure) concern (USEPA 2014a). In the 

absence of toxicity data, predicted acute and chronic toxicity values for the major transformation 

products of bicyclopyrone were estimated using EPA’s Ecological Structure Activity 

Relationships (ECOSAR) tool (v 1.11)5

 which is based on quantitative structure activity 

relationships (QSAR) for effects on fish, daphnids, mysids, and green algae. Predicted toxicity 

values were also generated for parent bicyclopyrone and compared to observed endpoints from 

registrant-submitted studies to assess confidence in ECOSAR predictions of the toxicity of 

bicyclopyrone’s transformation products. Based on the comparisons to parent, it was tentatively 

determined that only the transformation product CSCD656832 (SYN545680) might be a 

potential stressor of concern in the ecological risk assessment. However, based on its detections 

in laboratory studies, it was present mainly as a minor degradate in aerobic soil studies, reaching 

a level of ≥10% in only one of 16 soils studied. While it was also detected as a minor degradate 

in a soil photodegradation study, data from such studies are not used in aquatic exposure 

modeling. Additionally, in adsorption studies, the compound was only moderately mobile in one 

soil and slightly mobile in three soils. Thus, it was determined that it was highly unlikely that 

inclusion of CSCD656832 residues in aquatic exposure modeling would alter the risk 

conclusions. 

2.3. Receptors 

A receptor is a biological entity that is exposed to a stressor (USEPA 1998). For this assessment, 

the receptors include terrestrial and aquatic plants and animals inhabiting fields where 

bicyclopyrone is applied, and those inhabiting non-target areas to which bicyclopyrone may be 

transported (e.g., via spray drift and runoff). Consistent with the process described in the 

Overview Document (USEPA 2004), the risk assessment uses a surrogate species approach in its 

evaluation of bicyclopyrone. Toxicological data generated from surrogate test species, which are 

intended to be representative of broad taxonomic groups, are used to extrapolate to potential 

effects on a variety of species (receptors) included under these taxonomic groupings. 

2.4. Assessment Endpoints 

Assessment endpoints represent the actual environmental value that is to be protected, defined by 

 

5 http://www.epa.gov/oppt/newchems/tools/21ecosar.htm
-Page 12 of 88- 

an ecological entity (e.g., species, community) and its attributes (USEPA 1998). For 

bicyclopyrone, the ecological entities include birds, mammals, freshwater fish and invertebrates, 

estuarine/marine fish and invertebrates, terrestrial plants, insects, and aquatic plants and algae. 

The attributes evaluated for each of these entities may include growth, reproduction, and 

survival. 

2.5. Conceptual Model 

For a pesticide to pose an ecological risk, it must reach ecological receptors in biologically 

significant concentrations. An exposure pathway is the means by which a pesticide moves in the 

environment from a source to an ecological receptor. For an ecological pathway to be complete, 

it must have a source, a release mechanism, an environmental transport medium, a point of 

exposure for ecological receptors, and a feasible route of exposure. 

A conceptual model provides a description of the predicted relationships between bicyclopyrone, 

the potential routes of exposure, and the predicted effects for each assessment endpoint. 

2.5.1. Risk Hypothesis 

For bicyclopyrone, the following ecological risk hypothesis is employed for this risk assessment: 

Bicyclopyrone has high mobility in soil; it can move to surface water through spray drift 

and runoff, and it has potential to leach to ground water in vulnerable environments (e.g., 

high water tables, high rainfall/irrigation, sandy soils, etc.). Therefore, bicyclopyrone may 

produce adverse effects on survival, growth, and/or reproduction of aquatic plants and 

animals, may pose a chronic risk to small birds, terrestrial-phase amphibians, terrestrial 

plants, invertebrates, reptiles, and mammals. Bees and other pollinators may be at risk 

due to the systemic nature of the compound and the possibility that residues could be 

transported to pollen and nectar on which bees forage. To the extent to which terrestrial 

and/or aquatic plants are affected by the proposed uses of the herbicide, other taxa may be 

indirectly affected via direct effects on primary productivity and loss of habitat. 

2.5.2. Conceptual Model Pathways and Effects 

 

The environmental fate properties of bicyclopyrone indicate that for ground spray applications, 

spray drift, and runoff are potential transport mechanisms to aquatic habitats where non-target 

organisms may be exposed. It is expected that non-target terrestrial organisms can be exposed to 

bicyclopyrone following pre-emergent application, through consumption of exposed plants and 

invertebrates on the treated field. The plant uptake of the chemical may be a pathway of 

exposure to non-target terrestrial organisms upon consumption. Additionally, bicyclopyrone 

may reach terrestrial environments off treated fields via spray drift, and via application of 

irrigation groundwater containing residues of bicyclopyrone. A summary of the transport 

pathways and the models used to generate estimated environmental concentrations (EECs) for 

those pathways in the assessment is provided in Table 2.1.
-Page 13 of 88- 

 As bicyclopyrone is nonvolatile, atmospheric transport is not a major transport pathway. 

Additionally, the Screening Tool for Inhalation Risk (STIR) version 1.0 (November 23, 

2010) indicates that exposure via inhalation is not likely to be a risk concern for birds and 

mammals (Appendix E). Additionally, the low log Kow (-1.2) suggests that 

bicyclopyrone is not likely to bioconcentrate or bioaccumulate in aquatic or terrestrial 

organisms. With a log acid dissociation constant (pKa) of 3.06, bicyclopyrone will exist 

predominantly as an anion at environmental pH values in U.S. soils. Based on this as 

well as on submitted soil mobility data, bicyclopyrone is expected to be very highly 

mobile in soil. Therefore, bicyclopyrone has the potential to leach to groundwater. 

While bicyclopyrone does not have chemical properties that suggest strong partitioning to 

sediment, some chemical will inevitably move into benthic sediment pore water via 

diffusion. Potential risk to sediment-dwelling organisms due to exposure to 

bicyclopyrone in pore water is not evaluated in this assessment, but cannot be precluded. 

Bicyclopyrone may be applied using standard spraying equipment; thus spray drift is 

expected to result in exposure to organisms off of treated fields when broadcast 

applications of liquids occur in situations conducive to spray drift. 

 

The transport pathways may result in exposure to various aquatic and terrestrial organisms. With 

exposure, the following attribute changes have the potential to occur: 

 Effects to individual organisms, 

 Effects to food webs (reduction in prey and food, modification of primary constituent 

elements (PCE) related to prey availability), and 

 Effects to habitat integrity (reduction in primary productivity, reduced cover, community 

change, and modification of PCE related to habitat). 

Table 2.1. List of the various models and the related taxa for which the models will be used to assess risk. 

Environment Taxa of 

Concern 

Exposure 

Media 

Exposure 

Pathway 

Model(s) or 

Pathway Attribute Change 

Aquatic 

Vertebrates/ 

Invertebrates 

Surface water/ 

sediment 

Runoff and spray 

drift to water and 

sediment 

SWCC 

Individual 

Organisms 

Food Chain 

Habitat Integrity 

Aquatic Plants 

(vascular and 

nonvascular) 

Food Chain 

Habitat Integrity 

Riparian plants See terrestrial exposure pathways Habitat Integrity 

Terrestrial Vertebrate 

Dietary items 

Ingestion of 

residues in/on 

dietary items, 

including treated 

seeds as a result 

of direct 

application 

T-REX 

Individual 

Organisms 

Food Chain 

Habitat Integrity 

Consumption of 

aquatic organisms 

Residues taken 

up by aquatic 

organisms 

Not a major 

transport 

pathway 

--- 
-Page 14 of 88- 

Environment Taxa of 

Concern 

Exposure 

Media 

Exposure 

Pathway 

Model(s) or 

Pathway Attribute Change 

Plants 

Spray drift/runoff Runoff and spray 

drift to plants 

TERRPLANT 

AgDRIFT 

Individual 

Organisms 

Food Chain 

Habitat Integrity 

Surface water 

Residues in 

irrigation water 

leaching to 

groundwater 

SWCC 

Groundwater 

SCIGROW 

PRZM-GW 

Bees and other 

terrestrial 

invertebrates1 

Dietary items 

Spray contact 

and ingestion of 

residues in/on 

dietary items as 

a result of direct 

application. 

Uptake of 

pollen/nectar 

from plants. 

Multiple models

Individual 

Organisms 

Colony/Population 

Integrity 

All 

Environments All 

Movement through 

air to aquatic and 

terrestrial media 

Spray drift AgDRIFT (Spray 

drift) Individual 

Organisms 

Food Chain 

Atmospheric Habitat Integrity 

transport 

Not a major 

transport 

pathway 

Text in italics represent transport pathways that are not of concern. 1 See pollinator SAP white paper for full list of modeling approaches for evaluating exposure used in this assessment 

(USEPA 2012). 

2.6. Analysis Plan 

The analysis plan is the final step in the Problem Formulation. During this step, an assessment 

design is developed, the scope of the assessment is outlined, the methods for conducting the 

assessment are determined, measurements of effects and exposure to evaluate the risk hypothesis 

are delineated, and initial data gaps and assumptions required to address them are identified. 

2.6.1. Conclusions from Previous Risk Assessments 

As this is a new registration, there are no previous US EPA ecological risk assessments for 

bicyclopyrone. 

2.6.2. Identification of Data Gaps and Uncertainties 

In terms of environmental fate studies required to support the registration of bicyclopyrone, there 

are no data gaps for bicyclopyrone. With respect to data requirements to support the assessment 

of ecological effects, the submitted passerine study was classified as supplemental due to 

uncertainties regarding actual exposure as test birds exhibited regurgitation (MRID 47842078). 

In this study, mortality coincided with regurgitation at multiple treatment levels. 

No data have been submitted for chronic effects to estuarine/marine fish and invertebrates and 

would be beneficial to characterize the toxic effects of bicyclopyrone to these taxa. Therefore, 
-Page 15 of 88- 

an estuarine/marine invertebrate life-cycle test (OCSPP 850.1350) and an estuarine/marine fish 

early-life stage test (OCSPP 850.1400) are listed as data gaps. However, acute-to chronic ratios 

(ACRs) based on freshwater fish and invertebrate toxicity values have been calculated to 

estimate estuarine/marine fish and invertebrate toxicity values, respectively. 

Although data from the acute contact and oral toxicity tests with young adult honey bees indicate 

bicyclopyrone is practically non-toxic to bees on an acute exposure basis, there is uncertainty 

regarding the potential acute and chronic effects of the compound on honey bee larval 

development and survival as well as potential for chronic effects of adult bees. Since 

bicyclopyrone is a systemic herbicide, residues may be transported by the plant into pollen 

and/or nectar and represent a route of exposure for bees through ingestion of residues in 

pollen/nectar. 

2.6.3. Measures of Exposure 

Screening-level assessments are intended to be protective of wildlife on a national level, as 

opposed to being regionally or locally specific. Therefore, this assessment is not intended to 

represent a spatially- or temporally-specific analysis. Maximum application rates are used to 

model EECs. Measures of exposure are based on aquatic and terrestrial models (Table 2.1) that 

calculate EECs using maximum proposed application rates and methods. Groundwater is also 

assessed due to the leaching potential of bicyclopyrone and the potential to use groundwater as 

irrigation water on crops. As this is a new registration, there are currently no monitoring data for 

bicyclopyrone for comparison to model-generated surface water EECs. Limited groundwater 

data are available from multiple submitted Prospective Groundwater studies conducted outside 

of the United States. 

The Surface Water Concentration Calculator (SWCC, v 1.106, May, 2014) is used to generate 

EECs representing concentrations that may occur in surface water. The SWCC simulates 

pesticide transformation on and runoff from an agricultural field (in addition to loadings from 

spray drift), following applications to crops. The model then simulates resulting concentrations 

in an adjacent surface water body (i.e., the standard pond). 

Groundwater concentrations are estimated using the Screening Concentration in Ground Water 

(SCI-GROW, v. 2.3, 8/8/2003) model as well as the PRZM-GW model (Pesticide Root Zone 

Model for Groundwater, version 1.07), with the GW-GUI (Graphical User Interface, version 1.0, 

August 31, 2012). PRZM-GW is a one-dimensional leaching model that estimates the 

concentrations of pesticides in groundwater. It accounts for pesticide fate in the crop root zone 

by simulating pesticide transport and degradation through the soil profile after a pesticide is 

applied to an agricultural field. PRZM-GW permits the assessment of multiple years of pesticide 

application (up to 100 years) on a single site. Six standard scenarios, each representing a 

different region known to be vulnerable to groundwater contamination, are available for use with 

PRZM-GW for risk assessment purposes. SCI-GROW is a regression model used as a screening 

tool to estimate potential pesticide concentrations in vulnerable groundwater that might be used 

as drinking water. SCI-GROW was developed by fitting a linear model to groundwater 

concentrations with the Relative Index of Leaching Potential (RILP) as the independent variable. 

Groundwater concentrations were taken from 90-day average high concentrations from 
-Page 16 of 88- 

Prospective Ground Water studies; the RILP is a function of aerobic soil metabolism and the 

soil-water partition coefficient. 

The Terrestrial Residue Exposure Model (T-REX, version 1.5.2, 6/20/2013) is used to derive 

terrestrial EECs on food items for terrestrial vertebrates. Upper-bound Kenega nomogram 

values used in T-REX are based on Hoerger and Kenega (1972) as modified by Fletcher et al. 

(1994) are used to derive EECs for terrestrial mammals and birds based on dietary- and dosebased exposures from pre-emergent applications. A one-year time period is simulated. 

Consideration is given to different types of feeding strategies for mammals and birds, including 

herbivores, insectivores and granivores. For dose-based exposures, three weight classes of 

mammals (15, 35, and 1000 g) and birds (20, 100, and 1000 g) are considered. 

The TerrPlant model (v. 1.2.2, 12/26/2006) is used to derive runoff EECs for estimating 

exposures to terrestrial plants inhabiting dry and semi-aquatic areas. Exposure estimates using 

the Screening Tool for Inhalation Risk (STIR, v. 1.0, 11/23/2010) indicated that inhalation was 

not expected to be a significant route of exposure for wildlife (Appendix E). Exposure models 

are parameterized using relevant use (proposed label rates) and environmental fate data 

according to current EFED model input parameter guidance.6

To characterize potential non-target plant exposure from spray drift alone, Tier 1 modules in 

AgDRIFT (v. 2.1.1, December 2011) were used to estimate how far off-site spray drift exposure 

might occur at a level known to cause adverse effects in terrestrial plant toxicity studies. For 

ground applications, EFED used the American Society of Agricultural and Biological Engineers 

(ASABE, formerly ASAE) Very Fine-to-Fine droplet size category in its modeling. This size 

category is EFED’s default distribution when labels do not specify application parameters. The 

volume median diameter (Dv50) for the Very Fine-to-Fine droplet size distribution is 175 

microns. 

The Kow-based Aquatic BioAccumulation Model (KABAM)7 v. 1.0 is used to estimate potential 

bioaccumulation of hydrophobic organic pesticides in freshwater aquatic food webs and 

subsequent risks to mammals and birds via consumption of contaminated aquatic prey. 

However, KABAM modeling is not triggered by bicyclopyrone’s physicochemical 

characteristics and therefore is not used in this assessment. A waiver request for a fish 

bioaccumulation study was submitted by the registrant (MRID 47842117). The waiver request 

was granted because the chemical properties of bicyclopyrone indicate it is polar and would be 

expected to be lipophobic based on the Kow and solubility (the log Kow is 0.25, -1.2, and -1.9, at 

pH’s 5, 7, and 9 respectively). 

2.6.4. Measures of Effect 

Measures of effect are obtained from a suite of registrant-submitted guideline studies which are 

conducted with a limited number of surrogate species. The test species are not intended to be 

representative of the most sensitive species but rather are selected based on their ability to thrive 

under laboratory conditions. For example, toxicity testing reported in this risk assessment 

 

6 http://www.epa.gov/oppefed1/models/water/input_parameter_guidance.htm 7 http://www.epa.gov/oppefed1/models/water/kabam/kabam_user_guide.html
-Page 17 of 88- 

utilizes surrogate species to represent all freshwater fish (>2000 species) and birds (>680 

species) identified in the U.S. Open literature searches were not conducted to identify data for 

potential use in this risk assessment because bicyclopyrone is a new active ingredient. 

 

The acute measures of effect used in this screening-level assessment include the median lethal 

dose (LD50), median lethal concentration (LC50), and the median effect concentration (EC50). 

These are measures of acute toxicity which result in 50% of the respective effect in tested 

organisms. The endpoints for chronic measures of effect are the No Observed Adverse Effects 

Concentration (NOAEC) and the No Observed Adverse Effects Level (NOAEL). Toxicity 

studies are submitted for freshwater fish and invertebrates, estuarine/marine fish and 

invertebrates, aquatic and terrestrial plants, birds, mammals and honey bees. The measurement 

endpoints used for risk characterization are derived from studies which underwent review and 

are classified as “acceptable” (conducted under guideline conditions and considered to be 

scientifically sound) or “supplemental” (conditions deviated from guidelines but the results are 

scientifically sound). 

2.6.5. Integration of Exposure and Effects 

The exposure and effects data are integrated to evaluate the risks of adverse ecological effects on 

non-target species. For the screening-level assessment of bicyclopyrone, the deterministic, risk 

quotient (RQ) method is used to compare estimated exposure and measured toxicity values. The 

RQ method involves dividing EECs by the most sensitive acute and chronic toxicity values for 

specific taxa. The resulting RQs are then compared to the Agency’s levels of concern (LOCs) 

(USEPA 2004) for acute and chronic risk. These criteria are used to indicate if applications of 

bicyclopyrone, as directed on the proposed label, have the potential to cause adverse effects to 

non-target organisms. 

Although risk is often described in terms of the likelihood and magnitude of adverse effects, the 

risk quotient-based approach does not provide a quantitative estimate of likelihood or magnitude 

of an adverse effect, but rather provides a “yes” or “no” answer depending upon whether or not 

LOCs are exceeded. 
-Page 18 of 88- 

3. Analysis 

3.1. Use Characterization 

Bicyclopyrone is a new chemical proposed for use in controlling broad leaf weeds and annual 

grasses in corn in the U.S., at the maximum annual application rate of 0.045 lb a.i./A (50 g/ha). 

It is to be applied from pre-emergence through early post-emergence using standard ground 

spraying equipment. Based on label instructions, bicyclopyrone is generally to be applied once 

per season; however, a split application (i.e., pre-emergent and early post-emergent) that equates 

to the maximum recommended application/year (with a minimum 14-day re-application interval) 

may be used for corn grown for grain, seed or silage. 

Bicyclopyrone will be contained in one of two proposed products, a soluble concentrate (SC; 

18.1% a.i.; SYN-A16003 Herbicide; EPA Reg. No. 100-RUAA), and a Restricted Use product 

(RUP) consisting of a mixed formulation of a capsule suspension and suspension concentrate 

(CS and SC; 0.65% a.i.; SYN-A19707 Herbicide; EPA Reg. No. 100-RUAL). In the RUP, 

bicyclopyrone will be co-formulated with the other active ingredients mesotrione, atrazine, and 

S-metolachlor. The Canadian registration is for both products, while the Australian registration is 

for the SC only. As noted earlier, mesotrione has a common mode of action as bicyclopyrone, 

i.e., HPPD inhibition. 

Table 3.1. Summary of use information for the bicyclopyrone proposed use on corn.

Use 

Max. Single 

Applic. Rate 

(lbs a.i./A) 

Max. Seasonal 

Applic. Rate (lbs 

a.i./A) 

Seasonal Max. 

# of App. 

Min. App. 

Interval (d) EPA Reg. No. 

Corn (field corn, 

seed corn, silage 

corn, yellow popcorn 

and sweet corn)2

0.045 0.045 21

 14 100-RUAA 

(SYN-A16003) 

Corn (field corn, 

seed corn, silage 

corn, yellow popcorn 

and sweet corn) 

0.0453 0.0453 2 

Not stated, 

but 2nd

application 

must be postemergence 

100-RUAL 

(SYN-A19707; 

Restricted Use 

product) 

1

The typical use will be once per year (as modeled in this assessment), but the label allows for a split application up to the maximum annual 

application for corn grown for grain, seed or silage. 

2

Applications to sweet corn and yellow popcorn must be pre-emergent only. 3Single and seasonal rate for this product reduce to 0.0375 lb a.i./A 

for soils with an organic matter content of <3.5% (based on the atrazine component of the co-formulation). 

3.2. Exposure Characterization 

3.2.1. Environmental Fate and Transport 

Bicyclopyrone is a relatively soluble, nonvolatile compound that is stable to hydrolysis across all 

tested pH levels (MRID 47841919). Based on an acid dissociation constant (pKa) of 3.06, which 

indicates that approximately 50% of a compound will be ionized at an equivalent pH, with 

increasing percentages as pH increases, bicyclopyrone will exist predominantly as an anion 

(positively charged ion) at environmentally relevant pH values in U.S. soils, and available data 
-Page 19 of 88- 

indicate that adsorption is not correlated with soil organic matter. Based on this as well as on 

submitted soil mobility data, bicyclopyrone is expected to be very highly mobile in soil (MRIDs 

47842055, 47842056, 47842057, 47842059). Bicyclopyrone photodegrades on soil, with halflives ranging from 4 to 13 days (mean of 7.6; n=3; MRID 47842029). In laboratory studies 

conducted in darkness, it ranges from slightly persistent to persistent in aerobic soil, 

metabolizing to multiple organic transformation products and carbon dioxide. In the 12 domestic 

and European soils studied, aerobic soil metabolism half-lives ranged from 20 to 350 days (mean 

of 165 days), indicating a wide variation in persistence across soils (MRIDs 47842026, 

47842033, 47842034). In four Brazilian soils, all of which were acidic (pH range of 3.5-5.9), the 

half-life ranged from 82 to 434 days (mean of 243; MRID 47842035). The compound is stable 

in anaerobic soil and anaerobic aquatic systems (MRIDs 47842027, 47842073, 47842074), and 

is relatively stable in aerobic aquatic systems, with half-lives of 393-681 days (mean of 550; 

n=4) in the latter (MRIDs 47842073, 47842074). Although it only photodegrades slowly in 

water, with respective half-lives of 11 and 50 days at pH 5 and 7 buffered water, and 74.8 days in 

natural water (pH 7.3; MRID 47841921), and is relatively stable in aerobic aquatic systems, 

bicyclopyrone degraded with a half-life of roughly 7.5 days in a non-guideline aerobic aquatic 

metabolism study that was irradiated during the incubation (MRID 47842075). However, the 

significance of this result is unclear, and there were multiple uncertainties with the study that 

resulted in a classification of “reliable with restrictions.” 

Three of the transformation products of bicyclopyrone are characterized as very highly mobile in 

soil. The major transformation product CSCC163768 has Freundlich organic carbon-normalized 

coefficients (KFOCs) of 2.8 and 3.4 L/kg in two soils studied (MRID 47842062). Adsorption 

coefficients could not be quantitatively determined for the major transformation product 

SYN503780 and the minor transformation product CSAA806573 due to lack of adsorption 

(MRIDs 47842060, 47842061). The major transformation product CSCD656832 was moderately 

mobile in one soil and slightly mobile in three soils, with KFOCs of 247, 1340, 5179, 6180 L/kg 

(MRID 47842155). Structures and maximum concentrations for these and other transformation 

products are listed by study in Appendix B. 

In terrestrial field dissipation studies, bicyclopyrone was non-persistent, with dissipation halflives of 1.7-4.4 days in bare-ground plot studies conducted at three sites in the U.S. (MRIDs 

47842038, 47842039, 47842040). The application rate (0.196 lb a.i./A) used in the U.S. studies 

was over four times the currently proposed application rate for corn (and is slightly greater than 

the proposed U.S. application rate at the time the studies were conducted). However, 

concentrations of the pesticide in time 0 samples were 55%, 80% and 104% of the nominal 

application rate. Nine field studies conducted in Europe and one field study conducted in 

Australia were also submitted. Across all sites, the dissipation half-life was generally five weeks 

or less (see footnotes, Table 3.3). 

In the terrestrial field dissipation studies conducted in the U.S., limited leaching of bicyclopyrone 

and its transformation products was observed (Table 3.2), despite water inputs of 116-207% of 

the historical averages. Runoff was not monitored in the studies. Transformation products were 

a collective maximum of 23.2% (7 days) in the GA study, 20.4% (3 and 7 days; single degradate) 

in the IA study, and 14% (day 1; single degradate) in the NE study. Thus, while the parent 

rapidly dissipated from the surface soils, it was unclear what the predominant routes of 
-Page 20 of 88- 

dissipation were in each study. Based on laboratory data, aerobic soil transformation and 

photodegradation on soil are potentially major pathways of dissipation. It is noted that the major 

soil photolysis transformation product, SYN503780, was detected at all three sites. The 

registrant has submitted a non-guideline study (not formally reviewed) suggesting that parent 

compound transported below the surface may be wicked upward through evaporative transport 

flux in the soil and subsequently photodegraded on the surface soil. However, in that nonguideline study, the correlation between half-lives and total irradiance is poor (with and without 

accounting for water input during the first week), and it is noted that the maximum concentration 

for the photodegradate SYN503780 was observed at 1 day post-treatment in two of the three 

U.S. field studies, rather than further along in the studies as might be expected if such a wicking 

process was occurring. Additionally, the lack of detections of the parent compound or the very 

highly mobile degradate CSCC163768 at depths greater than 0-15 cm throughout the 536- to 

546-day studies may indicate that conditions may not have been conducive to leaching or the 

compound was degraded before leaching could occur. Water balance information was not 

reported for any of the U.S. terrestrial field dissipation studies. 

Table 3.2. Leaching Depths and Concentrations in U.S. Terrestrial Field Dissipation Studies 

Test System Apparent Major Route 

of Dissipation 

Maximum Concentrations and Depths 

(cm soil; days after application) 

Georgia 

Dothan soil series 

Sandy loam

pH 5.9

Transformation1

Soil 

Bicyclopyrone: 0.198 lb/A (0-15 cm; day-0) 

SYN503780: 0.015 lb/A (0-15 cm; 1 day) 

CSCD656832: 0.023 lb/A (0-15 cm; 21 days) 

CSCD642512: 0.005 lb/A (0-15 cm; 3 days) 

CSCC163768: 0.012 lb/A (0-15 cm; 3 days) 

CSAA806573: 0.004 lb/A (0-15 cm; 1 day) 

Iowa 

Clarion soil series 

Sandy loam

pH 7.4

Transformation to SYN503780 

Soil 

Bicyclopyrone: 0.141 lb/A (0-15 cm; day 0) 

SYN503780: 0.040 lb/A (0-15 cm; 3 and 7 days) 

Nebraska 

Hastings soil series 

Silt loam

pH 7.3 

Transformation to SYN503780 

Soil 

Bicyclopyrone: 0.105 lb/A (0-15 cm; day 0) 

SYN503780: 0.027 lb/A (0-15 cm; 1 day) 

CSAA806573: 0.007 lb/A (0-15 cm; 4 days) 

CSCD642512: 0.001 lb/A (0-15 cm; 120 days) 

Values are reviewer-calculated. Transformation products were converted into parent equivalents. Volatilization and 

run-off were not studied; leaching was not observed. 

Bicyclopyrone residues may move to groundwater via leaching, and may move to surface water 

bodies via spray drift and runoff of dissolved or (to a lesser extent) sediment-sorbed/associated 

residues (erosion). In aerobic soil metabolism studies conducted on two of the transformation 

products (rather than on parent), each was found to be non-persistent in aerobic soil, with halflives of 4.7-7.1 days for SYN503780 and <1 day for CSAA806573 (MRIDs 47843036, 

47843037). Laboratory metabolism and field studies also showed in general that persistence in 

the environment is not an expected issue for these transformation products. However, in 

prospective groundwater studies conducted in Europe following parent bicyclopyrone 

application, SYN503780 was detected in wells at sampling intervals up to 3 years after 
-Page 21 of 88- 

application (MRIDs 47842066, 47842067, 47842068, 47842069). 

Based on its hydrophilicity (Log Kow of -1.2 at pH 7), bicyclopyrone is not expected to 

bioaccumulate in aquatic or terrestrial organisms. Table 3.3 summarizes the physical/chemical 

properties of bicyclopyrone as reported by the registrant and based upon submitted 

environmental fate studies on the pesticide. 

Table 3.3. Chemical properties and environmental fate parameters of bicyclopyrone. 

Chemical 

Fate/Parameter Value Study Classification Source (MRID)/Comments 

IUPAC Name 

4-hydroxy-3-[2-(2-methoxyethoxymethyl)-6-

trifluoromethyl-pyridine-3-

carbonyl]-bicyclo[3.2.1]oct-3-

en-2-one 

̶ 

Chemical Formula C19H20F3NO5 ̶ 

Chemical Structure O CF3

N

OH O

O

OMe

̶ 

Molecular Mass (g/mol) 399.36 g/mole (C19H20F3NO5) ̶ Registrant-submitted phys/chem 

property values. 

Vapor Pressure (25°C) 

(Torr) 3.75 x 10-8 ̶

Registrant-submitted phys/chem 

property values (converted from 5 

· 10-6 Pa). 

Henry’s Law Constant 

(atm-m3

/mol; pH 7.2) 1.67 x 10-13 ̶

Registrant-submitted phys/chem 

property values (converted from 

1.7 . 10-8 Pa m3/mol) 

Solubility (20°C) (ppm) 

Pure water: 1.2 g/l (a pH of 

about 3 was recorded) 

Aqueous sol.: 38 g/L at pH 4.9

Aqueous sol.: 119 g/L at pH 7.2

Aqueous sol.: 119 g/L at pH 9.2 

̶ Registrant-submitted phys/chem 

property values. 

Octanol-water partition 

coefficient at 25°C (log 

Kow) 

At pH 5 log Kow = 0.25 

At pH 7 log Kow = -1.2 

At pH 9 log Kow = -1.9 

̶ Registrant-submitted phys/chem 

property values. 

Acid Dissociation 

Constant (pKa) at 20C 3.06 ̶ Registrant-submitted phys/chem 

property values. 

Hydrolysis half-life 

(pHs 5,7,9; 50 °C) Stable at pH 4, 5, 7, 9 Acceptable MRID 47841919 

Aqueous photolysis 

half-life 

11.1 days @ pH 5 

50.1 days @ pH7 

74.8 days in natural water @ pH 

7.3 

Supplemental MRID 47841921 

Soil photolysis half-life 4.4, 5.2, 13.3 days Supplemental MRID 47842029 
-Page 22 of 88- 

Chemical 

Fate/Parameter Value Study Classification Source (MRID)/Comments 

Aerobic soil 

metabolism half-life 

(20C) 

19.81

 days (same soil as in study 

below) Acceptable MRID 47842026 

350, 157, 331, 110, 335, 141, 

59.1 days Acceptable MRID 47842033 

53.5, 21.81(same soil as in study 

above), 266, 89, 68.4 days Acceptable MRID 47842034 

307, 81.9, 434, 148 days 

(Brazilian soils; values will not 

be used in this assessment) 

Supplemental MRID 47842035 

Not parent; for metabolite 

SYN503780: 4.7, 5.2, 7.1 days Supplemental MRID 47843036 

Not parent; for metabolite 

CSAA806573: <1 day (three 

soils) 

Supplemental MRID 47843037 

Anaerobic soil 

metabolism half-life 

(20C) 

Stable (half-life not calculated; 

no degradation during anaerobic 

phase) 

Acceptable MRID 47842027 

Aerobic aquatic 

metabolism half-life 

(20C) 

681, 393 days (2 systems) Acceptable MRID 47842073 

661, 466 days (2 systems) Acceptable MRID 47842074 

*NON-GUIDELINE* 

Aerobic aquatic 

metabolism with 

irradiation (metabolism 

+ photodegradation) 

half-life (20C) 

7.4, 7.5 days (2 systems) MRID 47842075 

Anaerobic aquatic 

metabolism half-life 

(20C) 

1423, 6244 (stable; 2 systems) Supplemental MRID 47842073 

1159, 2077 (stable; 2 systems) Supplemental MRID 47842074 

Freundlich soil-water 

partition coefficients 

(KF); Freundlich 

organic carbonnormalized coefficients 

(KFOC) 

Parent Bicyclopyrone

KF: 0.24, 0.83, 0.37, 0.45, 1.39, 

0.22, 0.35 L/kg 

KFOC: 39, 35, 31, 11, 32, 28, 7 

L/kg 

Acceptable MRID 47842055 

Parent Bicyclopyrone

KF: 1.34, 0.25, 0.20, 0.14, 1.39

L/kg 

KFOC: 46, 18, 10, 14, 87 L/kg 

Acceptable MRID 47842056 

Parent Bicyclopyrone

KF: 0.32, 1.74 L/kg 

KFOC: 29, 103 L/kg 

Acceptable MRID 47842057 
-Page 23 of 88- 

Chemical 

Fate/Parameter Value Study Classification Source (MRID)/Comments 

Parent Bicyclopyrone

KF: 0.11, 0.48, 0.29, 0.13, 0.91

L/kg 

KFOC: 7, 24, 59, 11, 61 L/kg 

Acceptable MRID 47842059 

Parent Bicyclopyrone 

(Brazilian soils) 

KF: 1.1, 6.3, 2.2, 26.6 L/kg 

KFOC: 46, 352, 241, 264 L/kg 

Supplemental MRID 47842058 

Degradate CSCC163768 

KF: 0.03, 0.08 L/kg 

KFOC: 2.8, 3.4 L/kg 

Values could not be determined 

due to lack of adsorption in two 

additional soils.

Acceptable MRID 47842062 

Degradate SYN503780 

Values could not be determined 

due to lack of adsorption (4 

soils). 

Acceptable MRID 47842060 

Degradate CSAA806573 

No values determined due to 

lack of adsorption (4 soils). 

Acceptable MRID 47842061 

Degradate CSCD656832

KF: 5.2, 38.9, 51.8, 98.9 L/kg 

KFOC: 247, 1340, 5179, 6180 

L/kg 

Acceptable MRID 47842155 

Terrestrial field 

dissipation half-life 

(bare soil; simulated 

corn use conditions)2

4.4 days GA Acceptable MRID 47842038 

5.0 days IA Acceptable MRID 47842039 

1.7 days NE Acceptable MRID 47842040 

1 The same soil was used in two studies. To prevent double-counting when determining the input values for modeling, the mean 

of these two (i.e., 20.8 days) is used to represent this soil rather than the two individual half-lives. 2Reported in the table only for 

fully reliable, domestic studies. In eight of the reviewed TFD studies (not all foreign studies were reviewed) conducted in 

Europe, half-lives were determined to be 3.52, 5.9, 10.6, 20.3, 31.5, 36.0, 24.6, and 3.6 days. 

Microbial degradation in aerobic soil and photodegradation in soil are likely to be the main 

pathways by which the compound transforms in the environment. 
-Page 24 of 88- 

Major transformation products of bicyclopyrone include: 

 CSCC163768 6-(trifluoromethyl)pyridine-2,3-dicarboxylic acid 

 SYN503780 (or CSAA794148) 2-(2-methoxy-ethoxymethyl)-6-trifluoromethyl-nicotinic 

acid 

 CSCD656832 3-hydroxy-6-(trifluoromethyl)pyridine-2-carboxylic acid 

 CSCD642512 2-[[3-(2,4-dioxobicyclo[3.2.1]octane-3-carbonyl)-6-(trifluoromethyl)-2-

pyridyl]methoxy]acetic acid 

 CSAA589691 (1S,3R)-cyclopentane-1,3-dicarboxylic acid

 carbon dioxide. 

Minor transformation products of bicyclopyrone include: 

 CSAA806573 2-hydroxymethyl-6-trifluoromethyl-nicotinic acid 

 CSAA915194 4-hydroxy-3-[2-(2-hydroxy-ethoxymethyl)-6-trifluoromethyl-pyridine-3-

carbonyl]-bicyclo[3.2.1]oct-3-en-2-one. 

A transformation product detected only in a single non-guideline study (i.e., the aerobic aquatic 

metabolism study conducted with irradiation) was: 

 CSAA456156 6-trifluoro-methyl-pyridine-3-carboxylic acid. 

Chemical structures, physical/chemical properties, and a summary of maximum and final 

detections of the degradates in the fate studies are provided in Appendix B.

To determine the potential for groundwater contamination, multiple Prospective Groundwater 

Studies (OCSPP 835.71008

) conducted in Europe were submitted to demonstrate the leaching of 

the compound in the field. A review of the studies indicated that they are reliable, but with 

restrictions (i.e., classified supplemental). All of the (European) studies had deficiencies relative 

to OCSPP 835.7100 guidance, such as using multiple rather than single applications, not 

installing wells in clusters, not screening at two soil depths, placing wells outside the perimeter 

of the test plot, insufficient water inputs, and not collecting soil samples and soil-pore water 

samples. None of the studies were conducted in the U.S. and all applications were made early 

post-emergence. Each of the studies is discussed below. 

In a study conducted in Germany, bicyclopyrone was broadcast applied as an emulsifiable 

concentrate (EC) formulation (A15749E/A15749F, containing nominal 150 g a.i./L) at a nominal 

rate of 0.18 lb a.i./A (equivalent to 200 g a.i./ha or 4 times the current proposed maximum 

application rate) annually from May 2007 to 2011 (MRID 47842066). Residues of bicyclopyrone 

were measured in all eight of the down-gradient wells studied. All wells were between 3.37 and 

3.93 m deep. Residues above the level of quantification (LOQ =0.01 μg/L) were first observed 

(0.04 μg/L) in wells closer to the point of application at 336-904 days post-treatment, and were 

observed in all down-gradient wells by 1247 days post-treatment. Residues of bicyclopyrone 

 

8

 USEPA. 2008. Fate, Transport and Transformation Test Guidelines. OCSPP 835.7100: Guidance for Prospective Ground-Water Monitoring 

Studies. Office of Chemical Safety and Pollution Prevention (OCSPP) formerly the Office of Prevention, Pesticides and Toxic Substances 

(OPPTS) (7101) EPA 712-B-10-001. August 25, 2008. http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0152-0044 
-Page 25 of 88- 

generally increased in all down-gradient wells throughout the study period, with maximum 

concentrations detected in each well ranging from 0.06 to 1.4 μg/L, and residues still detected at 

1478-1629 days post-treatment. Bicyclopyrone was not detected above the LOQ in up-gradient 

wells, with the exception of trace concentrations (0.01-0.02 μg/L) in one well following a wet 

summer period, and trace concentrations (0.02-0.09 μg/L) in two other wells following a dry 

spring. The transformation product SYN503780 was first detected in various down-gradient 

wells at 966 days (1 well), 1111 days (1 well), and 1399-1428 days (4 wells) days; residues were 

not detected above the LOQ in two wells during the study period. Maximum observed 

SYN503780 concentrations in water from wells B3-B8 were as follows: 0.04-0.11 μg/L at 1189-

1629 days. Residues of SYN503780 generally increased during the study period in one well to a 

maximum concentration (0.11 μg/L) at 1601-1629 days, and appeared to peak and decline to 

<LOQ (0.01 μg/L) in two other wells. A clear pattern of increase followed by decline was not 

observed in the other down-gradient wells. Residues of SYN503780 were not detected above the 

LOQ in any of the six up-gradient wells. 

In a study conducted in Hungary, bicyclopyrone was first detected in a shallow, down-gradient 

well at 0.02 μg/L at 726 days after the initial application, and was first detected in three other 

wells at 811-848 days (MRID 47842067). Bicyclopyrone was detected in one well at a maximum 

concentration of 0.24 μg/L at 848 days and declined to <LOQ (0.01 μg/L) by 1069 days. 

Bicyclopyrone was detected in two wells at ≤0.02 μg/Land had declined to <LOQ by 1134-1169 

days. Bicyclopyrone was not detected above the LOQ (0.01 μg/L) in the other seven wells 

studied. The only three monitoring wells with consistent detections of bicyclopyrone at >LOQ 

were all located down-gradient; however, bicyclopyrone was not detected above the LOQ in the 

pair of wells located directly down-gradient of the prevailing groundwater flow direction. 

Residues of the transformation product SYN503780 were not detected above the LOQ (0.01 

μg/L) in any wells. 

In a study conducted in France, residues of bicyclopyrone were only measured in four well 

clusters located down-gradient (MRID 47842068). Bicyclopyrone was first detected in each of 

the four shallow down-gradient wells at 306-951 days post-treatment and was a maximum of 

0.07 μg/L at 740 and 1195 days. Bicyclopyrone was first detected in each of the four downgradient deep wells at 404-951 days post-treatment, was a maximum of 0.11 μg/L at 951 days 

and was ≤0.06 μg/L at 1245 days post-treatment (residues detected in three shallow wells and 

two deep wells). The transformation product SYN503780 was generally only detected in one 

down-gradient well cluster, with residues first observed at the LOQ (0.01 μg/L) in both shallow 

and deep wells at 404-434 days, and residues detected at a maximum of 0.03 μg/L at 1043, 1103, 

and 1131 days in the shallow well. The transformation product SYN503780 was also detected 

once each in two shallow wells at the LOQ (0.01 μg/L; 740 and 951 days), and was detected 

twice in a deep well (at 951-986 days) at 0.01-0.02 μg/L. 

In a study conducted in Italy (MRID 47842069), bicyclopyrone was first observed in all six 

studied down-gradient wells between 188 and 353 days post-treatment. Bicyclopyrone residues 

were detected in separate wells at maxima of 0.04-0.34 μg/L (589-1053 days). Bicyclopyrone 

decreased to <LOQ (0.01 μg/L) by 836-1233 days post-treatment in three wells, and was 0.05-

0.13 μg/L in the other three studied wells by the end of the study (1254 days). The 

transformation product SYN503780 was initially detected in three of the down-gradient wells at 
-Page 26 of 88- 

the LOQ (0.01 μg/L) at 188-234 days, and was not detected at ≥LOQ in the remaining three 

down-gradient wells until 553-713 days. SYN503780 was detected in two wells at a maximum 

of 0.02 μg/L (713-746 days) and declined to <LOQ by 776-868. In two other wells, maximum 

SYN503780 concentrations were 0.12-0.15 μg/L (776 days) and declined to <LOQ (0.01 μg/L) 

by 953-986 days. In two wells, SYN503780 residues were a maximum at 0.17 μg/L (807-868 

days) and declined to ≤0.03 μg/L by the end of the study (1254 days). 

3.2.2. Aquatic Exposure 

Screening-level modeling was conducted to generate EECs of bicyclopyrone in surface and 

groundwater following a 7-day pre-emergent application on corn. Surface water modeling was 

conducted using SWCC with an application rate of 0.045 lb a.i./A, applied in a single ground 

spray application. Physical/chemical properties and environmental fate source data (from 

submitted studies) are presented in Table 3.3. Input fate parameters used in surface water 

modeling with SWCC are presented in Table 3.4. Scenarios modeled with SWCC are indicated 

in Table 3.5. Bare-ground applications were modeled with the soil incorporation depth set to 0 

cm. 

EECs for bicyclopyrone in groundwater used for irrigation purposes were generated based on 

maximum labeled use rates and fate input parameters, developed using current EFED Input 

Parameter Guidance9

 and EFED standard models. 

EECs in groundwater were also estimated using EFED’s groundwater model SCI-GROW. Input 

parameter values used for groundwater modeling with SCI-GROW are presented in Table 3.6. 

The output of SCI-GROW represents concentrations that might be expected to occur in shallow 

unconfined aquifers under sandy soils, which is representative of the groundwater most 

vulnerable to pesticide contamination. 

Groundwater EECs for bicyclopyrone were derived using the PRZM-GW model with the GWGUI. In PRZM-GW simulations, each of these standard scenarios was used. Input parameter 

values used for groundwater modeling with PRZM-GW are presented in Table 3.7. PRZM-GW 

output represents pesticide concentrations in vulnerable groundwater located directly beneath an 

agricultural field, following many years of pesticide application. 

Table 3.4. Input values for the SWCC model for bicyclopyrone1

. 

Input Parameter Value Source/comment 

Molecular weight (g/mol) 399.36 g/mol Registrant-submitted phys/chem property 

values. 

Vapor pressure (Torr @ 25 oC) 3.75 x 10-8 Registrant-submitted phys/chem property 

values (converted from 5 · 10-6 Pa). 

Solubility in water (mg/L @ 

20oC; pH 7.2) 119,000 Registrant-submitted phys/chem property 

values. 

Henry’s Law Constant (atmm3

/mol; pH 7.2) 1.67 x 10-13 Registrant-submitted phys/chem property 

values (converted from 1.7 . 10-8 Pa m3/mol). 

 

9 http://www.epa.gov/oppefed1/models/water/input_parameter_guidance.htm
-Page 27 of 88- 

Input Parameter Value Source/comment 

Hydrolysis half-life (t1⁄2 in days; 

pH 7) Stable MRID 47841919 

Aqueous Photolysis half-life (t1⁄2

in days; pH 7) 50.1 MRID 47841921 

Aerobic Soil metabolism half-life 

(t1⁄2 in days) 213.2 

MRIDs 47842026, 47842033, 47842034 

Represents the 90th percentile confidence 

bound on the mean of 12 half-lives (mean = 

165, SD = 122.14) 

Anaerobic aquatic metabolism 

half-life (t1⁄2 in days) stable MRIDs 47842073, 47842074 

Aerobic Aquatic metabolism 

half-life (t1⁄2 in days) 667.2 

MRIDs 47842073, 47842074 

Represents the 90th percentile confidence 

bound on the mean of 4 half-lives (mean = 550, 

SD = 142.81) 

Soil partition coefficient KFD 

(mL/goc) 0.59 

MRIDs 47842055, 47842056, 47842057, 

47842059 

Mean Kd (mean of 19 Kd values; ionic 

compound; adsorption not correlated with Koc) 1EFED input parameter guidance is located at: http://www.epa.gov/oppefed1/models/water/input_parameter_guidance.htm

Table 3.5. SWCC scenarios and inputs for bicyclopyrone modeling

Use SWCC Scenario Applic. Rate 

(lbs a.i./A) Applic. Dates Comments 

Corn 

CA_corn 

IA_corn 

IL_Corn 

IN_Corn 

KS_Corn 

MN_Corn 

MS_corn 

NC_cornE 

NC_cornW 

ND_corn 

NE_Corn 

OH_Corn 

PA_corn 

STX_corn 

TX_corn 

0.045 

(0.05 kg/Ha) 

Applied 7 days 

pre-emergence 

Single, pre-emergence 

application to soil 

surface by ground 

spray. 

Table 3.6. Input Values for the SCI-GROW model for bicyclopyrone. 

Variable Name Data Value 

Data Source 

MRID(s) Comment 

Application Rate (lbs. 

a.i./A/application) 0.045 Label ̶

Application Frequency 

(1/yr) 1 Label ̶

Aerobic Soil Metabolism 

Half-life (days) 125.5 

MRIDs 

47842026, 

47842033, 

47842034

Represents the median of 12 

aerobic soil metabolism halflife values.1
-Page 28 of 88- 

Variable Name Data Value 

Data Source 

MRID(s) Comment 

KFOC (mL/goc) 7 

MRIDs 

47842055, 

47842056, 

47842057, 

47842059

Lowest of 19 values (since 

there is >three-fold variation)1

1EFED input parameter guidance is located at: http://www.epa.gov/oppefed1/models/water/input_parameter_guidance.htm

Table 3.7. Input values for the PRZM-GW model for bicyclopyrone. 

Variable Name Data Value 

Data Source 

MRID(s) Comment 

Application Method Ground spray Label 

Application Date 7 days pre-emergence Label Single, pre-emergence 

application to soil. 

Application Rate 

(lbs. a.i./acre) [kg/ha] 0.045 [0.05] Label 

Application Frequency 1 Label 

Application Interval 

(days) NA 

Hydrolysis Half-life 

(days; pH 7.2) stable MRID 

47841919 

Aerobic Soil Metabolism 

Half-life (days) 213.2 

MRIDs 

47842026, 

47842033, 

47842034 

Represents the 90 

percent upper 

confidence limit on 

the mean of 12 

aerobic soil 

metabolism half-life 

values. 

KFD (mL/g) 0.59 

MRIDs 

47842055, 

47842056, 

47842057, 

47842059 

Mean of 19 KFD

values (ionic 

compound; adsorption 

not correlated with 

Koc) 

1EFED input parameter guidance: http://www.epa.gov/oppefed1/models/water/przm_gw/wqtt_przm_gw_input_guidance.htm

The EECs in Table 3.8 reflect the 1-in-10 year peak, 21-day and 60-day surface water 

concentrations. The SWCC modeled concentrations (μg/L) represent untreated surface water. 

The scenario with the maximum EEC (NE Corn) is bolded. The selected crop-specific scenarios 

are standard Agency-developed scenarios. Output files for SWCC are provided in Appendix C. 

Groundwater EECs are presented in Table 3.9. The SCI-GROW and PRZM-GW concentrations 

represent groundwater concentrations that might be expected in shallow, unconfined aquifers 

under sandy soils. Output files for the two groundwater models are provided in Appendix D. Of 

the two groundwater models, PRZM-GW estimated the highest residues based on Wisconsin 

central sands. To achieve breakthrough, an extended weather file of 100 years was used, as 

breakthrough to groundwater did not occur using the standard 30-yr modeling run. 
-Page 29 of 88- 

Table 3.8. Estimated environmental concentrations for bicyclopyrone use on corn. 

Crop Scenario Acute (1-in-10-

yr; ppb) 

21-day average (1-

in-10-yr; ppb) 

60-day average (1-

in-10-yr; ppb) 

Corn 

CA_corn 0.86 0.85 0.84 

IA_corn 1.03 1.03 1.03 

IL_Corn 1.98 1.96 1.92 

IN_Corn 2.25 2.26 2.28 

KS_Corn 3.11 3.09 3.03 

MN_Corn 1.92 1.91 1.88 

MS_corn 3.63 3.6 3.58 

NC_cornE 0.92 0.93 0.94 

NC_cornW 0.96 0.95 0.93 

ND_corn 1.65 1.65 1.65 

NE_Corn 4.04 4.01 3.92 

OH_Corn 2.02 2 1.97 

PA_corn 0.95 0.94 0.95 

STX_corn 2.24 2.21 2.15 

TX_corn 1.03 1.01 0.99 

Table 3.9. PRZM-GW and SCI-GROW groundwater EECs for bicyclopyrone use on corn. 

Model Crop Scenario 

Highest 

Daily 

Value 

(μg/L) 

Post 

Breakthrough 

Average 

(μg/L) 

Average 

Simulation 

Breakthrough 

Time (days) 

PRZM-GW Corn WI Central Sands/Corn 7.95 7.33 12,079 

SCI-GROW Corn NA 1.32 NA NA 

3.2.3. Terrestrial Exposure 

The proposed application of bicyclopyrone to crops has the potential to reach non-target 

terrestrial organisms via spray drift and runoff (for plants) and which may settle on plants and/or 

be taken up by plants as a result of systemic uptake and distribution. For terrestrial animals, TREX (version 1.5.2) is used to calculate dietary- and dose-based EECs of bicyclopyrone for 

mammals and birds feeding on the site of application. EECs are considered worst case and may 

be lower for split applications. Input values for T-REX include the maximum single application 

rates, number of applications, and retreatment interval for a given use and are located in Table 

3.1. In this assessment, EFED uses a default foliar dissipation half-life of 35 days as an input for 

terrestrial exposure modeling in T-REX. The default value is generally consistent with 

information from residue decline studies submitted by the registrant and reviewed by the EPA 

Office of Pesticide Programs’ Health Effects Division (HED; Global Joint Review Monograph 

B.7.6 Residues resulting from supervised trials [Annex IIA 6.3; Annex IIIA 8.3], 2011). 

Dietary- and dose-based exposure estimates from application of bicyclopyrone are presented in 

Table 3.10; output from T-REX is presented in Appendix G. 
-Page 30 of 88- 

Table 3.10. Terrestrial EECs as food residues for animals exposed to bicyclopyrone as a result of the proposed pre-emergent us

Food Type

Chronic Dietary 

Based 

(mg/kg diet) 

(mammals and 

birds) 

Dose Based (mg/kg bw) 

(birds)

Dose B(mg/k

(mam

All Size Classes Small (20 g) Medium (100 g) Large (1000 g) Small (15 g) Med

(35 

Corn; 0.045 lbs a.i./A; 1 application

Short grass 10.2 11.6 6.6 3.0 9.7 6.Tall grass 4.7 5.3 3.0 1.4 4.5 3.Broadleaf plants/small insects 5.7 6.5 3.7 1.7 5.5 3.Fruits/pods/large insects 0.6 0.7 0.4 0.2 0.6 0.Arthropods 4.0 4.6 2.6 1.2 3.8 2.Seeds (granivore) NA 0.2 0.1 0.0 0.1 0.N/A Not applicable. 
-Page 31 of 88- 

TerrPlant is used to calculate EECs for non-target plants that inhabit dry and semi-aquatic areas. 

In this assessment, EECs for non-target plants are calculated based on the potential runoff and 

spray drift of pre-emergent applications of bicyclopyrone (Table 3.11). TerrPlant does not 

account for particulate drift (Appendix H). 

Table 3.11. EECs for non-target terrestrial and semi-aquatic plants based on proposed use of bicyclopyrone 

(TerrPlant). 

Use(s) Application 

Technique 

Single Max. 

App. Rate 

(lbs a.i./A) 

EECs (lbs a.i./A) 

Semi-Aquatic 

Areas (Total) 

 Spray 

Drift 

Dry 

Areas 

(Total) 

Corn Ground spray 0.045 0.023 <0.001 0.003 

App. - Application. Max. - Maximum. N/A - Not applicable. 

To estimate exposure (i.e., EEC) to plants when groundwater contaminated with bicyclopyrone 

is applied to crops (irrigation water), EFED made the assumption that a field is irrigated with one 

inch of water containing residues. One acre has 6,272,640 cubic inches of water on the field. 

The 1-acre field with 1 inch of water has 3,630 cubic ft of water (6,272,640 x 0.00058 cubic 

ft/cubic inch). The field has 27,156 gallons of water (3,630 cubic ft x 7.481 gallons/cubic ft). 

Therefore, 1 inch of water on the 1-acre field weighs 226,625 lbs (27,156 gallons x 8.3453 

lbs/gallon of water). Using the maximum peak estimate of bicyclopyrone in groundwater from 

PRZM-GW (7.95 μg a.i./L) and based on the preceding assumptions, the EEC in terms of 

application rate (loading) is: 

 226,625 lb of water/acre x 7.95 μg/L = EEC = 0.0018 lbs a.i./A 

1,000,000,000 

Compared to EECs generated using TerrPlant, estimated residues in groundwater-derived 

irrigation water are roughly half those estimated for dry areas for runoff and spray drift 

combined (i.e., 0.003 lbs ai/A) and are 13 times lower that EECs estimated for semi-aquatic 

areas.

3.3. Ecological Effects Characterization 

3.3.1. Ecotoxicity Data 

Toxicity endpoints used in risk estimation and characterization for the proposed new use of 

bicyclopyrone are shown in Table 3.12 through Table 3.19. In the current risk assessment, the 

most sensitive endpoints available from registrant-submitted toxicity studies classified as 

acceptable or supplemental are the endpoints selected for quantitative use in risk estimation10. 

 

10 Only studies classified as “Supplemental” for quantitative use are used for risk quotient calculations in EFED assessments; supplemental 

studies that are not deemed useful for quantifying risks are used for risk characterization purposes only. 
-Page 32 of 88- 

As previously stated in Section 3.1, bicyclopyrone will be contained in one of two proposed 

products, a soluble concentrate (SC; 18.1% a.i.; SYN-A16003 Herbicide; EPA Reg. No. 100-

RUAA), and a Restricted Use product consisting of a mixed formulation of a capsule suspension 

and suspension concentrate (CS and SC; 0.65% a.i.; SYN-A19707 Herbicide; EPA Reg. No. 

100-RUAL). In the RUP, bicyclopyrone will be co-formulated with the other active ingredients 

mesotrione, atrazine, and S-metolachlor. The Canadian registration is for both products, while 

the Australian registration is for the SC only. As noted earlier, mesotrione has a common mode 

of action as bicyclopyrone, i.e., HPPD inhibition. However, ecotoxicity data were not submitted 

for the restricted use product. 

3.3.1.1. Aquatic Organisms 

Acute toxicity data for fish and aquatic invertebrates are summarized in Table 3.12 and Table 

3.13. Based on the available data, bicyclopyrone technical grade active ingredient (NOA449280 

TGAI) is classified as practically non-toxic to the freshwater rainbow trout (Oncorhynchus 

mykiss) and fathead minnows (Pimephales promelas), and to the estuarine/marine sheepshead 

minnows (Cyprinodon variegatus) on an acute exposure basis. For all of the freshwater and 

estuarine/marine fish tested (as well as aquatic-phase amphibians for which freshwater fish serve 

as surrogates), the acute 96-hr LC50 value exceeded the highest concentration tested, i.e, the 

acute toxicity estimates were non-definitive values at or close to the limit test concentration of 

100 mg a.i./L. Bicyclopyrone is practically non-toxic to the freshwater invertebrate water flea 

(Daphnia magna) and yielded a non-definitive endpoint (EC50>93.3 mg a.i./L); however, the 

compound is moderately toxic to estuarine/marine mysid shrimp (Americamysis bahia) and the 

Eastern oyster (Crassostrea virginica) on an acute exposure basis. The mysid shrimp was the 

most sensitive estuarine/marine invertebrate with an LC50 of 3.4 mg a.i./L. The solubility limit 

of bicyclopyrone (119 g/L at 20 °C) may be an important consideration in determining the 

toxicity classifications for non-definitive endpoints. 

Two acute toxicity tests were also carried out with the bicyclopyrone end-use formulation 

A16003E (containing 18.3% NOA449280 w/w) indicating that the formulation is slightly toxic 

to rainbow trout and D. magna on an acute exposure basis although for both species, the toxicity 

estimates were also non-definitive and were conducted to the limit test concentration of the 

formulation, i.e., the LC50 was >18.6 and 19.0 mg formulation/L for the rainbow trout and D. 

magna, respectively. However, it should be noted that acute toxicity tests with the formulation 

were not carried out with mysid shrimp or Eastern oyster, which are the most sensitive aquatic 

animals to bicyclopyrone TGAI. 

Toxicity endpoints for aquatic plants exposed to bicyclopyrone and its formulations are shown in 

Table 3.14. The freshwater vascular plant duckweed (Lemna gibba) was exposed to 

bicyclopyrone TGAI (MRID 47842095) over a 7-day period; the EC50 was determined to be 

0.013 mg a.i./L based on inhibition of frond yield. The empirical NOAEC in this study was 

determined to be 0.0032 mg a.i./L. 

The effects of bicyclopyrone TGAI (MRID 47842092) on the growth of the freshwater green 

alga (nonvascular plant), Pseudokirchneriella subcapitata, were tested; the 96-hour EC50 and 

empirical NOAEC were determined to be nominal concentrations of 2.4 and 1.0 mg a.i./L, 
-Page 33 of 88- 

respectively, based on decreased yield. Exposure of blue-green alga (Anabaena flos-aquae; 

MRID 47842093) to TGAI resulted in a 96-hour EC50 and empirical NOAEC of >94.8 and 94.8 

mg a.i./L, respectively, based on mean-measured test concentrations; therefore, at the exposure 

concentrations tested, bicyclopyrone TGAI had no inhibitory effect on the growth of the bluegreen alga. It should be noted the >94.8 mg a.i./L test concentration is the highest (limit) 

concentration in aquatic plant toxicity tests. 

The effects of bicyclopyrone TGAI on the toxicity to the freshwater diatom (Navicula 

pelliculosa; MRID 47842094) were tested; the 96-hour EC50 and empirical NOAEC were 

determined to be 9.8 and 2.39 mg a.i./L, respectively, based on mean-measured test 

concentrations and decreases in yield. The effects of bicyclopyrone TGAI on the toxicity to the 

marine diatom (Skeletonema costatum); MRID 47842102) were tested; the 96-hour EC50 and 

empirical NOAEC were determined to be 2.8 and 1.6 mg a.i./L, respectively, based on meanmeasured test concentrations and decreased yield. 

Two bicyclopyrone end-use products were tested on duckweed and green algae. Formulation 

A15749AD (150 g NOA449280/L EC formulation; 14.1% w/w a.i.) was tested on duckweed 

resulting in an EC50 and empirical NOAEC of 0.016 and 0.004 mg a.i./L, respectively, in a 7-day 

test (MRID 47842116). The most sensitive endpoint in that test was decreased biomass (dry 

weight yield). Formulation A16003E (end-use product of NOA449280 18.3% w/w) was tested 

on green algae resulting in an EC50 and empirical NOAEC of 2.0 and 0.59 mg a.i./L, 

respectively, in a 96-hour test with the most sensitive endpoint being decreased yield (MRID 

47842243). 

The effects of two transformation products of bicyclopyrone (MRIDs 47842149 and 47842139) 

were also tested on duckweed in a 7-day test. The two transformation products were 

CSAA589691 (metabolite of NOA449280; 85% pure) and CSCC163768 (metabolite of 

NOA449280; 98% pure). The EC50 using CSAA589691 was >0.09 mg a.i./L and the EC50 using 

CSCC163768 was >100 mg a.i./L. Given that the EC50 of TGAI bicyclopyrone (94.5% a.i.) for 

duckweed was 0.013 mg a.i./L, the data on the two degradates indicate that they are less toxic 

than the parent compound. 
-Page 34 of 88- 

Table 3.12. Acute toxicity endpoints used in risk estimation and characterization for freshwater organisms exposed to bicyclop

Study Type Species Test Material 

Endpoints 

(mg a.i./L) 

(Study Duration) 

Toxicity 

(St

Acute toxicity to 

freshwater vertebrates 

Rainbow trout 

(Oncorhynchus mykiss) 

NOA449280 TGAI 

(94.5%) 

LC50 >93.7 mg a.i./L 

 (96 hour test) 

Pr

A16003E 

(end-use product of 

NOA449280 18.3% w/w) 

LC50 >18.6 mg a.i./L 

 (96-hour limit test) 

Fathead minnow 

(Pimephales promelas) 

NOA449280 TGAI 

(94.5%) 

LC50 >93.4 mg a.i./L 

 (96 hour test) 

Pr

Acute toxicity to 

freshwater invertebrates 

Water flea 

(Daphnia magna) 

NOA449280 TGAI 

(94.5%) 

EC50 >93.3 mg a.i./L 

 (48-hour test) 

Pr

A16003E 

(end-use product of 

NOA449280 18.3% w/w) 

EC50 >19.0 mg a.i./L 

 (48-hour limit test) 

Table 3.13. Acute toxicity endpoints used in risk estimation and characterization for estuarine/marine organisms exposed to bi

Study Type Species Test Material 

Endpoints1

(mg a.i./L) 

(Study Duration) 

Toxicity 

(St

Acute toxicity to 

estuarine/marine fish 

Sheepshead minnow 

(Cyprinodon variegatus) 

NOA449280 TGAI 

(94.5%) 

LC50 > 123 mg a.i./L 

 (96 hour test) 

Pr

Acute toxicity to 

estuarine/marine 

invertebrates 

Mysid shrimp 

(Americamysis bahia) 

NOA449280 TGAI 

(94.5%) 

LC50 = 3.4 mg a.i./L 

 (96-hour test) 

Toxicity to 

estuarine/marine mollusks 

– shell deposition 

Eastern oyster 

(Crassostrea virginica) 

NOA449280 TGAI 

(94.5%) 

EC50 = 37 mg a.i./L 

 (96-hour test) 

1 Bolded values are the most sensitive endpoint(s) for a given taxonomic group and will be used in risk estimation. 
-Page 35 of 88- 

Table 3.14. Toxicity endpoints used in risk estimation and characterization for aquatic plants and algae exposed to bicyclopyron

Study Type Species Test Material Endpoints1 (mg a.i./L) 

(Stu

Toxicity to vascular 

aquatic plants 

Duckweed 

(Lemna gibba) 

NOA449280 TGAI 

(94.5%) 

EC50 = 0.013 mg a.i./L 

NOAEC = 0.0032 mg a.i./L 

LOAEC = 0.010 mg a.i./L 

(7-day semi-static test) 

I

A15749AD 

(150 g NOA449280/L EC 

formulation; 14.1% w/w ai)

EC50 = 0.0164 mg a.i./L 

NOAEC = 0.004 mg a.i./L 

LOAEC = 0.0126 mg a.i./L 

(7-day test) 

Most sen

(know

CSAA589691 

(metabolite of 

NOA449280; 85% pure) 

EC50 >90.28 mg a.i./L 

NOAEC = 90.28 mg a.i./L 

 (7-day test) 

No effec

CSCC163768 

(metabolite of 

NOA449280; 98% pure) 

EC50 >100.25 mg a.i./L 

NOAEC = 100.25 mg a.i./L 

 (7-day test) 

No effec

Toxicity to nonvascular 

aquatic plants 

Green algae 

(Pseudokirchneriella 

subcapitata) 

NOA449280 TGAI 

(94.5%) 

EC50 = 2.4 mg a.i./L 

NOAEC = 1.0 mg a.i./L 

LOAEC = 2.0 mg a.i./L 

(96-hour test) 

Most s

A16003E 

(end-use product of 

NOA449280 18.3% w/w) 

EC50 = 2.0 mg NOA449280/L 

NOAEC = 0.59 mg NOA449280/L 

LOAEC = 1.83 mg NOA449280/L 

(96-hour test) 

Most s

Toxicity to blue-green 

alga 

Blue-green alga (Anabaena 

flos-aquae) 

NOA449280 TGAI 

(94.5%) 

EC50 >94.8 mg a.i./L 

NOAEC = 94.8 mg a.i./L 

 (96-hour test) 

Most sens

Toxicity to the freshwater 

diatom 

Freshwater diatom (Navicula 

pelliculosa) 

NOA449280 TGAI 

(94.5%) 

EC50 = 9.8 mg a.i./L 

NOAEC = 2.39 mg a.i./L 

LOAEC = 5.10 mg a.i./L 

(96-hour test) 

Most s

Toxicity to the marine 

diatom 

Marine diatom (Skeletonema 

costatum) 

NOA449280 TGAI 

(94.5%) 

EC50 = 2.8 mg a.i./L 

NOAEC = 1.6 mg a.i./L 

LOAEC = 3.0 mg a.i./L 

(96-hour test) 

Most s

1 Bolded values are the most sensitive endpoint(s) for a given taxonomic group and will be used in risk estimation.
-Page 36 of 88- 

Freshwater Fish and Invertebrates: Chronic 

Chronic toxicity data for freshwater fish and aquatic invertebrates exposed to bicyclopyrone are 

summarized in Table 3.15. In a 33-day early life-stage toxicity test with fathead minnows 

exposed to bicyclopyrone TGAI (MRID 47842087), there were no statistically (p>0.05) or 

biologically significant effects for any measurement endpoint, which included hatchling success, 

larval survival, and growth yielding a NOAEC of 10 mg a.i./L and a LOAEC >10 mg a.i./L. In a 

21-day chronic life-cycle study with D. magna (MRID 47842091), the NOAEC and LOAEC 

were 103.7 and >103.7 mg a.i./L, respectively. Similar to the chronic endpoints for the fathead 

minnow, there were no statistically (p>0.05) or biologically significant effects for any 

measurement endpoint, which included hatchling success, larval survival, and growth. 

Estuarine/Marine Fish and Invertebrates: Chronic 

No chronic data have been submitted to the Agency for estuarine/marine fish or invertebrates. 

Using the available information and assuming the non-definitive endpoints in the acute and 

chronic freshwater and estuarine/marine fish studies are definitive, an acute-to-chronic (ACR) 

ratio was calculated. Based on the fathead minnow (Pimephales promelas) acute toxicity value 

of 93.4 mg ai/L and chronic value of 10.0 mg ai/L, the ACR is 9.34. Applying this ratio to the 

estuarine/marine sheepshead minnow (Cyprinodon variegatus) acute toxicity value of 123.0 mg 

ai/L, yields an estimated chronic toxicity endpoint of 13.2 mg ai/L. Similarly, using the 

available information and assuming the non-definitive endpoints in the acute and chronic 

freshwater and estuarine/marine invertebrate studies are definitive, an ACR value was derived. 

Based on the water flea (Daphnia magna) acute value of 93.3 mg ai/L and chronic NOAEC of 

103.7, the ACR is 0.90. Applying this ratio to the estuarine/marine mysid shrimp (Americamysis 

bahia) acute value of 3.4 mg ai/L results in an estimated estuarine/marine invertebrate NOAEC 

of 3.7 mg ai/L. 
-Page 37 of 88- 

Table 3.15. Chronic toxicity endpoints used in risk estimation and characterization for fish and aquatic invertebrates exposed t

Study Type Species Test Material Endpoints1 (mg a.i./L) 

(St

Early life stage toxicity to 

freshwater fish 

Fathead minnow 

(Pimephales promelas) 

NOA449280 TGAI 

(94.5%) 

NOAEC = 10 mg a.i./L 

LOAEC >10 mg a.i./L 

(33-day test) 

None ef

larva

Chronic toxicity to 

freshwater invertebrates 

Water flea 

(Daphnia magna) 

NOA449280 TGAI 

(94.5%) 

NOAEC = 103.7 mg a.i./L 

LOAEC >103.7 mg a.i./L 

(21-day test) 

None ef

larva

Estimated Sheepshead minnow (Cyprinodon variegatus) NA NOAEC = 13.2 mg a.i./L Estimated 

to-chro

fa

Estimated Mysid shrimp (Americamysis bahia) NA NOAEC = 3.7 mg a.i./L Estimated 

to-chroni

1 Bolded values are the most sensitive endpoint(s) for a given taxonomic group and will be used in risk estimation. 
-Page 38 of 88- 

3.3.1.2. Terrestrial Organisms 

Birds and Mammals: Acute and Sub-Acute 

Acute toxicity data for birds and mammals exposed to bicyclopyrone are summarized in Table 

3.16. Based on the available data, bicyclopyrone is classified as slightly-to-moderately toxic to 

birds (bobwhite quail, Colinus virginianus; canary, Serinus canaria) on an acute oral exposure 

basis and practically non-toxic to bobwhite quail and mallard duck (Anas platyrhynchos) on a 

subacute dietary exposure basis. Since birds serve as a surrogate for terrestrial-phase amphibians 

and reptiles, bicyclopyrone is classified as moderately toxic on an acute oral exposure basis and 

practically non-toxic on a subacute dietary exposure basis for these taxa. The avian acute oral 

toxicity studies with the bobwhite quail and mallard showed signs of sublethal toxicity including 

ruffled appearance of treated birds, lethargy, loss of coordination, prostration, lower limb 

weakness, and convulsions. An acute oral toxicity study with the canary resulted in a more 

sensitive LD50 (MRID 47842078); however, regurgitation was observed in the study and 

mortality was prevalent among birds that that had regurgitated. Therefore, the study is classified 

as supplemental and cannot be used for quantitative risk assessment purposes. There are no data 

available describing the effects of any bicyclopyrone formulations to the canary. The subacute 

studies with the bobwhite quail and mallard ducks provided no evidence of toxicity at any 

dietary concentration tested. 

The acute oral toxicity of one bicyclopyrone end-use product was tested on bobwhite quail. 

Formulation A16003E (end-use product of NOA449280 18.3% w/w) was tested resulting in an 

LD50 of 425 mg a.i./kg bw in a 14-day test (MRID 47842250) classified as moderately toxic. No 

regurgitation was observed in any treatment group; however clinical signs of toxicity among 

treatment groups included ruffled appearance of treated birds, loss of coordination, lethargy, 

lower limb weakness, and reduced reaction to external stimuli. 

Bicyclopyrone is classified as practically nontoxic to mammals on an acute oral exposure basis. 

No mortality was observed at the limit dose (5000 mg/kg bw) in an acute oral toxicity study with 

the rat (Rattus norvegicus), which was the most sensitive mammalian species tested; therefore, 

the 96-hr LD50 is non-definitive, i.e., LD50>5,000 mg a.i./kg bw. HED has concluded that 

bicyclopyrone exhibits low acute toxicity to mammals by all exposure routes (EPA Toxicity 

Category III or IV). 

Terrestrial Invertebrates 

Acute toxicity data for adult honey bees are summarized in Table 3.17; however, no data are 

available for evaluating the effects on adult bees from chronic exposure, nor are data available to 

evaluate acute or chronic effects on honey bee larvae. Additional non-guideline acute toxicity 

data on non-target terrestrial arthropods exposed to bicyclopyrone are considered supplemental 

information in the current risk assessment and are also summarized in Table 3.17. Additional 

non-target arthropods typically not included in current risk assessments include the predatory 

mite (Typhlodromus pyri), the parasitoid wasp (Aphidius rhopalosiphi), and earthworm (Eisenia 
-Page 39 of 88- 

foetida) all of which are routine species used in the Organization for Economic Cooperation and 

Development (OECD) test guidelines. 

Bicyclopyrone TGAI and formulation A16003E (end-use product of NOA449280 18.3% w/w) 

are practically non-toxic to young adult honey bees on an acute oral and contact exposure basis 

with LD50>200 and 212 μg a.i./bee, respectively (48-hour tests; MRIDs 47842096 and 

47842248). The earthworm was exposed to bicyclopyrone TGAI (94.5%) and formulation 

A16003E with no observable adverse effects in either study at any of the concentrations tested, 

i.e., LC50>1000 mg a.i./kg soil (MRIDs 47842098 and 47842249). The predatory mite was 

exposed to formulation A15749AD (150 g NOA449280/L EC, 14.1% w/w) with no observable 

adverse effects at any concentration tested, i.e., LC50>0.18 lbs a.i./A (47842118). The parasitic 

wasp was exposed to formulations A15749AD and A15936Z (an EC formulation containing 80 

g/L NOA449280 and 400 g/L S-metolachlor). In the study with A15749AD (MRID 47842097) 

the lethal residue resulting in 50% mortality (LR50) was a treatment rate of 0.005 lbs a.i./A based 

on mortality and decreased reproduction. The study using A15936Z resulted in no observable 

effects at any concentration tested, i.e., LR50>0.179 lbs a.i./A (MRID 47842150).
-Page 40 of 88- 

Table 3.16. Acute toxicity endpoints used in risk estimation and characterization for birds and mammals exposed to bicyclopyr

Study Type Species Test Material Endpoints1 Tox

Acute oral toxicity to birds 

Bobwhite quail

(Colinus virginianus) 

NOA449280 TGAI 

(94.5%) 

LD50 = 1206 mg a.i./kg bw 

14-day test 

A16003E 

(end-use product of 

NOA449280 18.3% 

w/w) 

LD50 = 425.11 mg a.i./kg bw 

 (14-day test) 

Canary 

(Serinus canaria) 

NOA449280 TGAI 

(94.5%) 

LD50 = 209 mg a.i./kg bw 

14-day test 

Subacute dietary toxicity to birds 

Bobwhite quail

(Colinus virginianus) 

NOA449280 TGAI 

(94.5%) 

LC50 >5820mg a.i./kg diet 

(LD50 > 1495 mg/kg bw/day) 

8-day test

Mallard duck 

(Anas platyrhynchos) 

NOA449280 TGAI 

(94.5%) 

LC50 >5550 mg/kg diet 

(LD50 >3020 mg/kg bw/day) 

8-day test 

Acute oral toxicity to mammals3 HanRcc:WIST (SPF) rats (Rattus norvegicus) NOA449280 TGAI (94.5%) LD50 >5000 mg/kg bw 

1 Bolded values are the most sensitive endpoint(s) for a given taxonomic group and will be used in risk estimation. 2 Endpoints cannot be used in risk estimation due to regurgitation in the passerine study. It will be listed as a data gap. 3 Mammalian toxicity data were reviewed by OPP Health Effects Division (U.S. EPA) as part of the Global Joint Review for bicyclopyrone. 

Table 3.17. Acute toxicity endpoints used in risk estimation and characterization for terrestrial invertebrates exposed to bicyclo

Study Type Species Test Material Endpoints1 Tox

Acute contact and oral toxicity to 

honey bees 

Honey bee 

(Apis mellifera) 

NOA449280 TGAI 

(94.5%) 

LD50 >200 g a.i./bee (contact) 

LD50 >212.2 g a.i./bee (oral) 

(48-hour test) 

Pr

A16003E (end-use 

product of 

NOA449280 18.3% 

w/w) 

LD50 >197.0 g a.i./bee (contact) 

LD50 >195.2 g a.i./bee (oral) 

(48-hour test) 

Pr

Acute contact 14-day toxicity to 

earthworms 

Earthworm 

(Eisenia foetida) 

NOA449280 TGAI 

(94.5%) 

LC50 >1000 mg a.i./kg soil 

 (14-day test) 
-Page 41 of 88- 

Study Type Species Test Material Endpoints1 Tox

A16003E (end-use 

product of 

NOA449280 18.3% 

w/w) 

LC50 >1000 mg a.i./kg soil 

 (14-day test) 

Acute contact 7-day toxicity to 

the predatory mite 

Predatory mite 

(Typhlodromus pyri) 

A15749AD (150 g 

NOA449280/L EC, 

14.1% w/w) 

7-d LR50 >200 g ai/ha (>0.18 lbs a.i./A) 

 (7-day test) 

Acute contact 48-hr toxicity to 

parasitic wasp 

Parasitic wasp 

(Aphidius rhopalosiphi) 

A15749AD (150g 

NOA449280 /L EC, 

14.1% w/w) 

LR50 = 6.0 g ai/ha (0.005 lbs a.i./A) 

 (48-hour test) 

A15936Z (an EC 

formulation 

containing 80 g/L 

NOA449280 and 400 

g/L S-metolachlor) 

LR50 >0.179 lbs a.i./A 

(>200 g a.i./ha) 

 (48-hour test) 

1LR50 = Lethal body residues resulting in 50% mortality 
-Page 42 of 88- 

3.3.1. Terrestrial Organism and Mammalian Chronic Endpoints 

Birds and Mammals: Chronic 

Chronic laboratory toxicity data for birds and mammals exposed to bicyclopyrone are 

summarized in Table 3.18. In a 21-week avian reproduction study with bobwhite quail exposed 

to bicyclopyrone in the diet, there was a statistically significant (5%; p>0.05) decrease in eggs 

cracked/hen, eggs cracked/eggs laid, hatchlings/egg set, hatchings/live 3-week embryos, and 14-

day old survivors/egg set at 640 mg ai/kg diet (NOAEC/LOAEC 200/640 mg ai/kg diet; 

19.1/60.1 mg ai/kg bw; MRID 47842082). In the same study at 2000 mg ai/kg diet reported 

significant effects included viable embryos/egg set, live 3-week embryos/viable embryos, and 

14-day old survivors/hen. 

In a 21-week avian reproduction study with the mallard exposed to bicyclopyrone in the diet, 

there was a statistically significant (5%; p>0.05) decrease in hatchlings/live 3-week embryos, 14-

day old survivors/hatchling, and 14-day old survivors/egg set (NOAEC/LOAEC 70/140 mg ai/kg 

die; 9.1/17.1 mg ai/kg bw; MRID 47842084). 

In both of the avian reproduction studies there was uncertainty in the biological relevance of 

some of the measurement endpoints since there was no apparent dose-response relationship. For 

the bobwhite quail, no dose-response was observed for mean hatching weight even though a 

statistically significant effect was detected across multiple dietary treatment levels. Likewise, in 

the mallard study, no dose-response was observed for eggs laid/hen and mean 14-day old 

survivors weight even though a statistically significant effects were detected. Although there 

was a slight dose-response for mean hatchling weight, the highest bicyclopyrone concentration 

showed the lowest difference in weight compared to controls while the lowest bicyclopyrone 

concentration had the greatest difference in weight. In both avian reproduction studies there 

appeared to be considerable variability in control birds making it difficult to detect treatment 

effects. Due to these uncertainties, the studies are classified as supplemental. 

In a rat 2-generation study evaluated by HED (MRID 47842127) ocular effects, decreases in 

offspring body weights and weight gains, and reproductive effects were observed. The parental 

LOAEL was 25 ppm (2.15/2.65 [M/F]) based on ocular effects (corneal opacity and vascular 

keratitis P and F1 males) and an increased incidence of pelvic dilation of the kidney (F0 and F1 

males and F1 females). Based on decreases (13.4% in males, 11% in females) in absolute body 

weights and body weight gains and in increased incidence of litters with vascular keratitis in the 

F1 and F2 generations, the offspring LOAEL was 500 ppm (43.65/52.7 mg/kg/day [M/F]). The 

offspring NOAEL was 25 ppm (2.15/2.65 mg/kg/day [M/F]). Based on reproductive parameters 

(changes in sperm parameters i.e., velocity of actual path, straight line velocity, and 

miscellaneous abnormalities, and a decrease in pre-coital interval), the reproductive LOAEL is 

5000 ppm (435.5/534 mg/kg/day [M/F]) and the reproductive NOAEL is 500 ppm (43.65/52.7, 

mg/kg/day [M/F]). 
-Page 43 of 88- 

Table 3.18. Chronic toxicity endpoints used in risk estimation and characterization for terrestrial animals exposed to bicyclopy

Study Type Species Test Material Endpoints1 

Avian reproduction

Bobwhite quail

(Colinus virginianus)

NOA449280 TGAI 

(94.5%)

NOAEL=19.1 mg a.i./kg bw/day

(200 mg a.i./kg diet)

LOAEL =60.1 mg a.i./kg bw/day

(640 mg a.i./kg diet)

21-week test

E

e

Mallard duck 

(Anas platyrhynchos) 

NOA449280 TGAI 

(94.5%) 

NOAEL=9.1mg a.i./kg bw/day 

(70 mg a.i./kg diet) 

LOAEL = 17.1 mg a.i./kg bw/day 

(140 mg a.i./kg diet) 

21-week test 

sur

d

Chronic toxicity to mammals2 – 

two-generation reproduction 

Wistar Han IGS Rat 

(Crl:WI (Han)) 

(Rattus norvegicus) 

NOA449280 TGAI 

(94.5%) 

NOAEL = 2.15 mg/kg bw/day 

(25 ppm) 

LOAEL = 43.65 mg/kg bw/day 

(500 ppm) 

D

in

in 

1 Bolded values are the most sensitive endpoint(s) for a given taxonomic group and will be used in risk estimation. 2 Mammalian toxicity data were reviewed by OPP Health Effects Division (U.S. EPA) as part of the Global Joint Review for bicyclopyrone. 3 Increased vascular keratitis in F1 and F2 generations was observed in the study but will not be used as the endpoint in risk estimation. Risk estimation will be based on 

 body weight gains. 
-Page 44 of 88- 

3.3.2. Terrestrial Plants 

Terrestrial Plant Seedling Emergence and Vegetative Vigour 

Toxicity data for terrestrial plants exposed to bicyclopyrone formulation A15749F (a 

NOA449280 EC formulation with 150 g a.i./L) are shown in Table 3.20. A 21-day seedling 

emergence study (MRID 47842103) was carried out on eleven terrestrial plant species (seven 

dicotyledonous [dicot] and four monocotyledonous [monocot] species) exposed to A15749F at 

multiple treatment rates. There were statistically significant (p<0.05) inhibitions in biomass for 

sunflower (Helianthus annuus), cucumber (Cucumis sativa), and cabbage (Brassica oleracea), 

biomass and height for turnip (Brassica rapa) and ryegrass (Lolium perenne), and plant survival 

and shoot height for onion (Allium cepa). The most sensitive monocot was ryegrass with an 

inhibitory concentration for 25 percent of the plants tested (IC25) and NOAEC of 0.073 and 

0.067 lbs a.i./A, respectively based on decreased biomass. The most sensitive dicot was cabbage 

with an IC25 and NOAEC of 0.005 and 0.002 lbs a.i./A, respectively, based on decreased 

biomass. The most sensitive seedling emergence endpoints for plant species exposed to 

bicyclopyrone can be seen in Table 3.20. 

Table 3.19. Toxicity endpoints used in risk estimation and characterization for terrestrial and semi-aquatic 

plants exposed to bicyclopyrone. 

Study Type Test Material Most Sensitive 

Species 

Endpoints 

(lbs ai/A) 

Effects 

(MRID) 

(Study 

Classification) 

Terrestrial 

plant toxicity: 

Tier II 

seedling 

emergence 

A15749F (a 

NOA449280 

EC formulation 

with 150 g 

a.i./L) 

Monocot: ryegrass 

(Lolium perenne) 

IC25 = 0.074 lbs a.i./A 

(82.4 g a.i./ha) 

NOAEC = 0.067 lbs a.i./A 

(75 g a.i./ha) 

LOAEC = 0.134 lbs a.i./A 

(150 g a.i./ha) 

Biomass 

(47842103) 

(Acceptable) 

Dicot: cabbage 

(Brassica 

oleracea) 

IC25 = 0.005 lbs a.i./A 

(6 g a.i./ha) 

NOAEC = 0.002 lbs a.i./A 

(2.4 g a.i./ha) 

LOAEC = 0.004 lbs a.i./A 

(4.7 g a.i./ha) 

Biomass 

(47842103) 

(Acceptable) 

Terrestrial 

plant toxicity: 

Tier II 

vegetative 

vigor 

A15749F (a 

NOA449280 

EC formulation 

with 150 g 

a.i./L) 

Monocot: onion 

(Allium cepa) 

IC25 = 0.02 lbs a.i./A 

(22.5 g a.i./ha) 

NOAEC = 0.017 lbs a.i./A 

(18.75 g a.i./ha) 

LOAEC = 0.03 lbs a.i./A 

(37.5 g a.i./ha) 

Biomass 

(47842104) 

(Acceptable) 

Dicot: sunflower 

(Helianthus annus) 

IC25 = 0.001 lbs a.i./A 

(0.92 g a.i./ha) 

NOAEC = 0.0002 lbs a.i./A 

(0.31 g a.i./ha) 

LOAEC = 0.001 lbs a.i./A 

(0.93 g a.i./ha) 

Biomass 

(47842104) 

(Acceptable) 
-Page 45 of 88- 

Table 3.20: Most sensitive 21-day seedling emergence endpoints for plant species exposed to bicyclopyrone

Species 

Latin name (common name) 

ER25 NOER 

Relative 

Sensitivity 

(g a.i./ha)

Most 

Sensitive 

Endpoint 

NOER 

(g a.i./ha)

Most 

Sensitive 

Endpoint 

Zea mays (corn) > 1200 NA 1200 NA

Helianthus annuus (sunflower) 258.75 Height 150 Biomass 

Allium cepa (onion) 105.15 Height 150 Survival, Height 

Avena sativa (oat) > 150 NA 150 NA

Glycine max (soybean) > 150 NA 150 NA

Cucumis sativa (cucumber) 45.9 Biomass 37.5 Biomass 

Lolium perenne (ryegrass) 82.35 Biomass 75 Biomass, Height 

Linum usitatissimum (flax) > 75 NA 75 NA

Lycopersicon esculentum (tomato) 29.8 Biomass 37.5 NA

Brassica rapa (turnip) 8.64 Biomass 9.375 Biomass, Height 

Brassica oleracea (cabbage) 6 Biomass 2.34 Biomass 

A 21-day vegetative vigour study (MRID 47842104) was carried out on eleven terrestrial plant 

species (seven dicot and four monocot species) exposed to A15749F at multiple treatment rates. 

There were statistically significant (p<0.05) inhibitions in biomass for corn (Zea mays), 

sunflower, ryegrass, oats (Avena sativa), cucumber, cabbage and turnip. There were statistically 

significant (p<0.05) inhibitions in plant biomass and shoot height for onion, and soybean 

(Glycine max), tomato (Lycopersicon esculentum), and flax (Linum usitatissimum). The most 

sensitive monocot was onion with an IC25 and NOAEC of 0.02 and 0.017 lbs a.i./A, respectively 

based on decreased biomass. The most sensitive dicot was sunflower with an IC25 and NOAEC 

of 0.001 and 0.0002 lbs a.i./A, respectively, based on decreased plant biomass. The most 

sensitive seedling emergence endpoints for plant species exposed to bicyclopyrone can be seen 

in Table 3.21.
-Page 46 of 88- 

Table 3.21: Most sensitive 21-day vegetative vigor endpoints for plant species exposed to bicyclopyrone

Species 

Latin name (common name) 

ER25 NOER 

Relative 

Sensitivity 

(g a.i./ha)

Most 

Sensitive 

Endpoint 

NOER 

(g 

a.i./ha)

Most 

Sensitive 

Endpoint 

Zea mays (corn) 530.7 Biomass 300 Biomass 

Lolium perenne (ryegrass) 142.8 Biomass 75 Biomass 

Avena sativa (oat) 46.5 Biomass 18.75 Biomass 

Linum usitatissimum (flax) 25.35 Biomass 8.34 Height 

Allium cepa (onion) 22.5 Biomass 18.75 Height, Biomass 

Brassica oleracea (cabbage) 13.55 Biomass 8.34 Height, Biomass 

Cucumis sativa (cucumber) 5.69 Biomass 2.78 Biomass 

Glycine max (soybean) 3.33 Biomass 2.78 Height, Biomass 

Brassica rapa (turnip) 1.45 Biomass 0.93 Biomass 

Lycopersicon esculentum (tomato) 1.46 Biomass 0.93 Height, Biomass 

Helianthus annuus (sunflower) 0.92 Biomass 0.31 Height, Biomass 

3.3.3. Incident Reports 

Bicyclopyrone has no existing registrations in North America; therefore, this assessment assumes 

that there are no existing incident reports associated with bicyclopyrone use in the United States. 

4. Risk Characterization 

Toxicity data and exposure estimates for bicyclopyrone are used to evaluate the potential for 

adverse ecological effects on non-target species. This screening-level assessment employs a 

deterministic risk estimation method, based on RQ values, to provide a metric of potential risks 

(Section 4.1). The potential for risk is further characterized in the Risk Description (Section 4.2) 

based on the risk estimation results and other relevant information about toxicity and ecosystems 

potentially at risk, and the environmental fate and transport characteristics of bicyclopyrone. In 

cases where an RQ value exceeds the listed species LOC, the potential for risk to listed species is 

characterized in greater detail in Section 5. 

4.1. Risk Estimation 

Unitless RQ values are compared to the Agency’s LOCs to identify taxonomic groups potentially 

at risk of acute or chronic effects associated with the proposed new use of bicyclopyrone. 

4.1.1. Aquatic Organisms 

As shown in 

Table 4.1 through Table 4.3, none of the RQ values calculated for the bicyclopyrone TGAI 

either approach or exceed the Agency’s LOCs for risk to non-listed species of fish and 

invertebrates or aquatic plants. Chronic RQ values for estuarine/marine fish and invertebrates 

are based on chronic toxicity values estimated using an ACR. Based on the 60-day and 21-day 
-Page 47 of 88- 

surface water concentrations the values for estuarine/marine fish and invertebrates, respectively, 

the NOAEC would need to be less than 0.004 mg/L (4 μg/L) in order for there to be a chronic 

risk of concern to estuarine/marine fish and invertebrates. EECs are reported for parent only 

(refer to Section 3.2.2). 

Table 4.4 through Table 4.6 summarize RQ values for aquatic vascular and nonvascular plants. 

Further characterization of the potential for adverse effects to aquatic organisms, based on the 

available data, is provided as part of the Risk Description in Section 4.2.1. Two exceedances 

were observed for listed plants for bicyclopyrone TGAI and formulation A15749AD in Table 

4.4 and Table 4.5, respectively (note: data are not available for formulation A14749AD on listed 

or non-listed nonvascular plants). 

Table 4.1. Acute and chronic RQ values for freshwater fish and invertebrates exposed to bicyclopyrone TGAI 

in surface water. 

Use 

App 

Rate 

lbs a.i./A 

(#app) 

App 

Method 

EECs

(mg/L)

RQ Values 

Freshwater Fish 

LC50=93.4 mg/L 

(TGAI) 

 NOAEC=10 mg/L

Freshwater 

Invertebrate 

EC50=93.3 mg/L 

(TGAI) 

NOAEC=103.7 μg/L

Peak 21-d 60-d Acute Chronic Acute Chronic 

Corn 0.045 

(2) 

Ground 

spray 

0.004 0.004 0.004 <0.01 <0.01 <0.01 <0.01 

RQ=peak EEC/LC50 (acute) or 21-day (invert) or 60-day (fish) EEC/NOAEC (chronic). 

The acute risk to listed species LOC (RQ≥0.05); the acute risk to non-listed species LOC (RQ≥0.5); the chronic risk LOC (RQ≥1) 

Table 4.2. Acute and chronic RQ values for freshwater fish and invertebrates exposed to bicyclopyrone TEP 

(A16003E) in surface water. 

Use 

App 

Rate 

lbs a.i./A 

(#app) 

App 

Method 

EECs

(mg/L)

RQ Values 

Freshwater Fish 

LC50=18.6 mg/L 

(TEP) 

 NOAEC=NA

Freshwater 

Invertebrate 

EC50=19.0 mg/L (TEP) 

NOAEC=NA

Peak 21-d 60-d Acute Chronic Acute Chronic 

Corn 0.045 

(2) 

Ground 

spray 

0.004 0.004 0.004 <0.01 NA <0.01 NA 

NA Not applicable. 

RQ=peak EEC/LC50 (acute) or 21-day (invert) or 60-day (fish) EEC/NOAEC (chronic). 

The acute risk to listed species LOC (RQ≥0.05); the acute risk to non-listed species LOC (RQ≥0.5); the chronic risk LOC (RQ≥1) 

Table 4.3. Acute and chronic RQ values for estuarine/marine fish and invertebrates exposed to bicyclopyrone 

TGAI in surface water. 

Use 

App 

Rate 

lbs a.i./A 

(#app) 

App 

Method 

EECs

(mg/L)

RQ Values 

Estuarine/Marine 

Fish 

LC50=123 mg/L 

(TGAI) 

 NOAEC=13.71

Estuarine/Marine 

Invertebrate 

EC50=3.4 mg/L (TGAI) 

NOAEC=3.71

Peak 21-d 60-d Acute Chronic Acute Chronic 

Corn 0.045 

(2) 

Ground 

spray 

0.004 0.004 0.004 <0.01 <0.01 <0.01 <0.01 
-Page 48 of 88- 

NA Not applicable. 1

 Based on ACRRQ=peak EEC/LC50 (acute) or 21-day (invert) or 60-day (fish) EEC/NOAEC (chronic). 

The acute risk to listed species LOC (RQ≥0.05); the acute risk to non-listed species LOC (RQ≥0.5); the chronic risk LOC (RQ≥1) 

Table 4.4. RQ values for listed and non-listed vascular and nonvascular aquatic plants exposed to 

bicyclopyrone TGAI in surface water as a result of spray drift only, based on maximum application rates for 

corn. 

Use 

App 

Rate 

lbs a.i./A 

(#app) 

App 

Method 

EECs 

(mg/

L)

RQ Values 

Vascular Plants 

EC50=0.013 mg/L 

NOAEC=0.003 mg/L

Nonvascular Plants 

EC50=2.4 mg/L 

NOAEC=1.0 mg/L

Peak Listed Non-listed Listed Non-listed 

Corn 0.45 

(2) 

Ground 

spray 

0.004 1.3 0.31 <0.01 <0.01 

Bold values exceed the plant LOC 1.0 

RQ = EEC/EC50 for non-listed species; EEC/NOAEC for listed species 

Table 4.5. RQ values for listed and non-listed vascular aquatic plants exposed to bicyclopyrone TEP 

(A15749AD) in surface water as a result of spray drift only, based on maximum application rates for 

corn. 

Use 

App Rate 

lbs a.i./A 

(#app) 

App Method 

EECs 

(mg/L)

RQ Values 

Vascular Plants 

EC50=0.016 mg/L 

NOAEC=0.004 mg/L

Peak Listed Non-listed 

Corn 0.45 

(2) Ground spray 0.004 1.0 0.25 

Bold values exceed the plant LOC 1.0 

RQ = EEC/EC50 for non-listed species; EEC/NOAEC for listed species 

Table 4.6. RQ values for listed and non-listed nonvascular aquatic plants exposed to bicyclopyrone 

TEP (A16003E) in surface water as a result of spray drift only, based on maximum application rates 

for corn. 

Use 

App Rate 

lbs a.i./A 

(#app) 

App Method 

EECs 

(mg/L)

RQ Values 

Nonvascular Plants 

EC50=2.0 mg/L 

NOAEC=0.59 mg/L

Peak Listed Non-listed 

Corn 0.45 

(2) Ground spray 0.004 <0.01 <0.01 

Bold values exceed the plant LOC 1.0 

RQ = EEC/EC50 for non-listed species; EEC/NOAEC for listed species 

4.1.2. Terrestrial Organisms 

In this assessment, acute oral, sub-acute dietary, and chronic RQ values are calculated for birds 

(Table 4.7) and acute oral and chronic RQ values for mammals (Table 4.8 and Table 4.9). 

In the bobwhite quail reproduction study, the most sensitive endpoints were eggs cracked/hen, 

eggs cracked/eggs laid, hatchlings/egg set, hatchings/live 3-week embryos, and 14-day old 

survivors/egg set resulting in a NOAEC/LOAEC of 200/640 mg ai/kg diet (19.1/60.1 mg ai/kg 
-Page 49 of 88- 

bw). Eggshell thickness was reported as not being significantly different from controls at any 

treatment level. In the mallard duck reproduction study, the most sensitive endpoints were 

hatchlings/live 3-week embryos, 14-day old survivors/hatchling, and 14-day old survivors/egg 

set resulting in a NOAEC/LOAEC of 70/140 mg ai/kg diet (9.1/17.1 mg ai/kg bw). 

 

For the pre-emergent use of bicyclopyrone on corn the acute dose-based RQ values for birds are 

below the Agency’s LOCs for acute risk to listed (RQ≥0.1) and non-listed (RQ≥0.5) species 

(Table 4.7). Chronic avian data shown in the table is for the most sensitive species, i.e., mallard; 

70 mg ai/kg diet). Furthermore, as can be seen in Table 6.1, no exceedances were found using 

the highest bicyclopyrone concentration in either of the avian reproduction studies (Mallard; 35 

mg ai/kg diet). Therefore, the reported NOAEL/LOAEL is 200/640 mg ai/kg diet and 70/140 

mg ai/kg diet for the Bobwhite quail (MRID 47842082) and Mallard (MRID 47842084), 

respectively. 

Table 4.7. Acutea avian, sub-acute dietary, and chronic,b dietary-based RQ values for TGAI bicyclopyrone. 

Corn 0.045 lbs a.i./A; 1 application 

Dietary Category Acute RQs Sub-Acute RQs Chronic RQs 

Short Grass 0.01 <0.01 0.15 

Tall Grass 0.01 <0.01 0.07 

Broadleaf plants 0.01 <0.01 0.08 

Fruits/pods/seeds <0.01 <0.01 0.01 

Arthropods 0.01 <0.01 0.06 

Granivore <0.01 NA NA 

NA=Not applicable 

a

Acute risk LOC exceeded for listed species is 0.1. 

b

Chronic risk LOC exceeded for listed and non-listed species is 1.0. 

The acute dose-based RQ values for mammals are below the Agency’s LOC for acute risk to 

listed (RQ≥0.1) and non-listed (RQ≥0.5) species (Table 4.8). However, chronic dose-based RQ 

values exceed the chronic risk LOC (RQ >1; Table 4.9) for small (15 g) and medium (35 g) 

sized mammals that consume short grass and broadleaf plants. No chronic risk LOCs are 

triggered by consumption of tall grass, fruits/pods/seeds, or arthropods, or by large mammals 

(1000g) consuming any food source. 

Table 4.8. Acute mammalian dose-based RQ values for proposed pre-emergent use of bicyclopyrone on corn.1,2 

Application 

Rate lbs a.i./A 

#app/interval 

(d) 

Body 

Weight 

(g) 

RQs for Corn 

Short Grass Tall Grass Broadleaf Plants Fruits/Pods/Seeds Arthropods 

0.045 

2/14

Small 

(15g) <0.01 <0.01 <0.01 <0.01 <0.01 

Medium 

(35g) <0.01 <0.01 <0.01 <0.01 <0.01 

Large 

(1000g) <0.01 <0.01 <0.01 <0.01 <0.01 

1 The acute risk to listed species LOC for mammals is 0.1 

2 The acute risk to non-listed species LOC for mammals is 0.5. 
-Page 50 of 88- 

Table 4.9. Chronic mammalian dose-based RQ values for proposed pre-emergent use of bicyclopyrone on corn.1

Application 

Rate lbs a.i./A 

#app/interval 

(d) 

Body 

Weight 

(g) 

RQs for Corn 

Short Grass Tall Grass Broadleaf Plants Fruits/Pods/Seeds Arthropods 

0.045 

2/14

Small 

(15g) 2.1 0.9 1.2 0.1 0.8

Medium 

(35g) 1.8 0.8 1.0 0.1 0.7

Large 

(1000g) 0.9 0.4 0.5 0.1 0.4 1Bolded values exceed the chronic LOC for listed and non-listed mammals (1) 

For terrestrial plants, RQ values (Table 4.10 and Table 4.11) for the pre-emergent use on corn 

are calculated based on the most sensitive toxicity endpoints from the submitted seedling 

emergence tests. RQ values for listed non-listed species of monocot plants are below the LOC 

for all areas as a result of runoff and spray drift and for spray drift alone. RQ values for nonlisted dicots in semi-aquatic areas exceed the Agency’s LOC for risk to plants. RQ values for 

listed dicots exceed the Agency’s LOC for plants in dry and semi-aquatic areas due to exposure 

from runoff and spray drift combined, as well as for exposure from spray drift alone. Tables 

4.12 and 4.13 list RQ values for corn based on the use of irrigation water. RQ values for listed 

and non-listed dicots exceeded the Agency’s LOC for risk to plants using groundwater-derived 

irrigation water. Conclusions regarding potential risk to listed and non-listed terrestrial plants, as 

they relate to RQ values based on the available NOAEC values, are discussed in Section 4.2. 

Table 4.10. RQ values for non-listed species1 of non-target terrestrial and semi-aquatic plants based on 

bicyclopyrone on corn (TerrPlant).

Use 

Dry Area 

RQs 

Semi-Aquatic Area 

RQs 

Spray Drift Only 

RQs 

Monocot Dicot Monocot Dicot Monocot Dicot 

Corn <0.1 0.54 0.31 4.59 <0.1 0.45 

Bolded values exceed the Agency’s level of concern (LOC) for risk to listed and non-listed species of terrestrial plants (RQ > 1). 1Seedling emergence IC25 and NOAEC monocot values are 0.074 and 0.067, and IC25 and NOAEC dicot values are 0.005 and 

0.002. Vegetative vigor IC25 and NOAEC monocot values are 0.02 and 0.017, and IC25 and NOAEC dicot values are 0.001 and 

0.0002. 

Table 4.11. RQ values for listed species1 of non-target terrestrial and semi-aquatic plants based on 

bicyclopyrone on corn (TerrPlant).

Use 

Dry Area 

RQs 

Semi-Aquatic Area 

RQs 

Spray Drift Only 

RQs 

Monocot Dicot Monocot Dicot Monocot Dicot 

Corn <0.1 1.35 0.34 11.48 <0.1 2.25 

Bolded values exceed the Agency’s level of concern (LOC) for risk to listed and non-listed species of terrestrial plants (RQ > 1). 1Seedling emergence IC25 and NOAEC monocot values are 0.074 and 0.067, and IC25 and NOAEC dicot values are 0.005 and 

0.002. Vegetative vigor IC25 and NOAEC monocot values are 0.02 and 0.017, and IC25 and NOAEC dicot values are 0.001 and 

0.0002. 
-Page 51 of 88- 

Table 4.12. Seedling Emergence RQ values for listed and non-listed species1

 of non-target plants based on 

bicyclopyrone on corn using groundwater-derived irrigation water.

Use 

Monocot: ryegrass (Lolium perenne) Dicot: cabbage (Brassica oleracea) 

IC25 = 0.074 lbs a.i./A NOAEC = 0.067 lbs a.i./A IC25 = 0.005 lbs a.i./A NOAEC = 0.002 lbs a.i./A 

Corn 0.02 0.03 0.36 0.9 

Bolded values exceed the Agency’s level of concern (LOC) for risk to listed and non-listed species of terrestrial plants (RQ > 1). 1RQ values are based on the irrigation water EEC of 0.0018 lbs a.i./A / the seedling emergence IC25 (non-listed) or NOAEL 

(listed) value. 

Table 4.13. Vegetative vigor RQ values for listed and non-listed species1 of non-target plants based on 

bicyclopyrone on corn using groundwater-derived irrigation water.

Use 

Monocot: ryegrass (Lolium perenne) Dicot: cabbage (Brassica oleracea) 

IC25 = 0.02 lbs a.i./A NOAEC = 0.017 lbs a.i./A IC25 = 0.001 lbs a.i./A NOAEC = 0.0002 lbs a.i./A 

Corn 0.09 0.11 1.8 9.0 

Bolded values exceed the Agency’s level of concern (LOC) for risk to listed and non-listed species of terrestrial plants (RQ > 1). 1RQ values are based on the irrigation water EEC of 0.0018 lbs a.i./A / the vegetative vigor IC25 (non-listed) or NOAEL (listed) 

value. 

To characterize potential non-target plant exposure from spray drift alone, Tier 1 modules in 

AgDRIFT (v. 2.1.1, December 2011) were used to estimate how far off-site spray drift exposure 

might occur at a level known to cause adverse effects in terrestrial plant toxicity studies. For 

ground applications, EFED used the American Society of Agricultural and Biological Engineers 

(ASABE, formerly ASAE) Very Fine-to-Fine droplet size category in its modeling. This size 

category is EFED’s default distribution when labels do not specify application parameters. The 

Dv50 for the Very Fine-to-Fine droplet size distribution is 175 microns. 

Table 4.14. Possible Effects Distance for Nontarget Terrestrial Plants Exposed to Bicyclopyrone through 

Spray Drift Only Based on the Most Sensitive Crop Species in Submitted Toxicity Studies. 

Crop 

Single Max. 

App. Rate 

(lbs a.i./A) 

AgDRIFT 

Scenario 

Distance from Treatment Site (feet) 

Monocots 

(non-listed) 

Onion 

IC25 = 

0.02 lbs a.i./A 

Monocots 

(listed) 

Onion 

NOAEL 

0.017 lbs a.i./A 

Dicots 

(non-listed) 

Sunflower 

IC25 = 

0.001 lbs a.i./A 

Dicots 

(listed) 

Sunflower 

NOAEL = 

0.0002 lbs a.i./A 

Corn1 0.045 Ground spray 6.6 6.6 111.6 456 

1While the max application rate during the growing season is 0.045 lbs a.i./A, it can be applied as a split dose during the growing 

season. 

Although the Agency does not typically quantify risk to non-target terrestrial invertebrates using 

the RQ method, acute toxicity studies with the young adult honey bee demonstrate that 

bicyclopyrone is practically non-toxic to young adult honey bees on an acute oral and an acute 

contact exposure basis (LD50 >11 μg a.i./bee). The potential for risk to non-target terrestrial 

organisms, associated with the proposed pre-emergent and early post-emergent use of 

bicyclopyrone on corn, is discussed further in the Risk Description (Section 4.2.2). There is 

uncertainty regarding the potential acute and chronic effects of the compound on honey bee 

larvae as well as potential for chronic effects of adult. Since bicyclopyrone is a systemic 

herbicide, residues may be present in pollen and/or nectar and represent a route of exposure for 
-Page 52 of 88- 

bees through both contact and ingestion. Therefore, there is uncertainty with respect to the 

likelihood of adverse effects from acute or chronic exposure of larval bees to residues that may 

be translocated to pollen/nectar. 

4.2. Risk Description and Conclusions 

This assessment evaluates the potential for ecological risks associated with the proposed use of 

the new herbicide bicyclopyrone as a pre-emergent or early post-emergent ground spray on corn. 

Bicyclopyrone is a selective, systemic herbicide of the HPPD-inhibitor class. The compound is 

stable to hydrolysis, but degrades on soil by photolysis (non-persistent) and aerobic 

biodegradation (slightly persistent to persistent). With a pKa of 3.06, bicyclopyrone will exist 

predominantly as an anion at environmentally relevant pH values, and is expected to be very 

highly mobile in soil and likely to move into surface and groundwater. Bicyclopyrone 

photodegrades slowly in water, but biodegrades in aquatic systems at a negligible rate. 

4.2.1. Aquatic Organisms 

RQ values are calculated for estimating acute and chronic risk to fish and aquatic invertebrates, 

where the submitted ecotoxicity data are sufficient to use in risk estimation. Aquatic animal and 

plant toxicity data reported in Section 3.3.1.1 and EECs are both reported in similar units, i.e.,

mg/L. For the proposed use of bicyclopyrone, acute and chronic RQ values are below the listed 

(RQ≥0.05) and non-listed (RQ≥0.1) species acute and chronic (RQ≥1.0) risk LOCs for all 

assessed fish and aquatic invertebrates based on toxicity of the TGAI. RQ values for the 

formulated product TEP A16003E, tested only in acute studies on freshwater fish and 

invertebrates, were below LOCs. However, using TGAI, chronic NOAEC values would need to 

be ≤0.004 mg a.i./L to listed and non-listed estuarine/marine fish and invertebrates for 

exceedances to occur. 

While TGAI bicyclopyrone had no LOC exceedances (RQ≥1) for nonvascular plants and nonlisted vascular plants, it did have an exceedance for listed vascular plants. Likewise, TEP 

formulation A15749AD had an LOC exceedance for listed vascular plants, but not for non-listed 

vascular plants. The formulation A16003E had no exceedances for listed or non-listed 

nonvascular plants. Based on submitted data, vascular plants are more sensitive to 

bicyclopyrone than are nonvascular plants (EC50=0.0013 mg/L for duckweed compared to an 

EC50=2.0 mg/L for green algae). Between nonvascular species (green algae, blue-green algae, 

freshwater diatom, and marine diatom), toxicity values i.e., EC50 values, were roughly similar 

(range 2.0-9.8 mg/L) except for blue-green algae which had an EC50 >94.8 mg/L. 

4.2.2. Terrestrial Organisms 

Acute and sub-acute RQ values calculated for dose-based risk to birds (and reptiles and 

terrestrial-phase amphibians for which birds serve as surrogates) indicate no LOC exceedances 

although there is uncertainty regarding passerine species. If the passerine data were to be used, 

there would be an exceedance to listed species (LOC >0.1) for small birds feeding on short grass. 

No chronic risk LOC is exceeded based on the avian toxicity data although there is some 

uncertainty with the bobwhite quail and mallard duck reproduction studies. For the bobwhite 
-Page 53 of 88- 

quail study, a dose-response was not observed for mean hatching weight even though a 

statistically significant effect was indicated for the endpoint. Likewise, in the mallard study, a 

dose-response was not observed for eggs laid/hen and mean 14-day old survivors weight even 

though a statistically significant effect was observed. Also, there was a slight dose-response 

effect in mean hatchling weight of mallards; however, the highest bicyclopyrone concentration 

showed the lowest difference compared to controls while the lowest bicyclopyrone concentration 

had the greatest difference. In both avian reproduction studies there appeared to be considerable 

variability in control birds making it difficult to detect treatment effects. 

Acute laboratory tests with terrestrial insects (i.e., honey bee) have demonstrated that 

bicyclopyrone is practically non-toxic to adult honey bees on an acute oral and contact exposure 

basis, although there is uncertainty regarding the potential chronic effects on adult bees and acute 

and chronic effects on larvae. 

The RQ values in Section 4.1 demonstrate that pre-emergent use of bicyclopyrone on corn may 

result in chronic risk to mammals (RQ>1.0). Although bicyclopyrone is classified as practically 

non-toxic to mammals on an acute oral exposure basis, chronic RQ values indicate the potential 

for adverse effects. The submitted two-generation reproduction study in rats indicated toxicity at 

25 mg/kg bw/day resulting in decreased absolute body weights and body weight gains (an 

increased vascular keratitis in F1 and F2 generations was also observed). The chronic risk LOC 

was triggered for small and medium-sized mammals that consume short grass and broadleaf 

plants. No LOC exceedances were observed with large mammals. No LOC exceedances for 

acute dose-based exposure to mammals of any size category. In order to get below the chronic 

risk LOC for small and medium-sized mammals, the application rate would need to decrease 

from 0.045 to 0.021 lbs a.i./A (roughly half). 

RQ values for listed and non-listed species of monocot plants are below the LOC for dry and 

semi-aquatic areas exposed through runoff and spray drift combined as well as through spray 

drift alone. RQ values for non-listed dicots in semi-aquatic areas exceed the LOC for risk to 

terrestrial plants. RQ values for listed dicots exceed the LOC for dry and semi-aquatic areas 

exposed through runoff and spray drift combined, as well as through spray drift alone. RQ 

values for listed and non-listed dicots exceed the Agency’s LOC for risk to plants using 

irrigation water based on data from vegetative vigor studies alone. Irrigation water LOC’s were 

not exceeded for monocots and dicots based on the seedling emergence data, or for monocots 

based on vegetative vigor study data. Based on submitted data, the most sensitive monocot in 

seedling emergence and vegetative vigor, i.e., ryegrass and onion, respectively, were roughly an 

order of magnitude less sensitive than the most sensitive dicot species, cabbage and sunflower. 

4.2.3. Conclusions 

Based on this screening-level assessment, the physicochemical properties of bicyclopyrone 

indicate that the herbicide has the potential to reach aquatic environments, including surface and 

ground water following pre-emergent applications. The available ecotoxicity data demonstrate 

that bicyclopyrone is practically-to-moderately nontoxic to fish and aquatic invertebrates and 

LOCs were not exceeded. Using TGAI bicyclopyrone or A16003E, chronic NOAEC values 

would need to be ≤0.004 mg a.i./L to listed and non-listed estuarine/marine fish and invertebrates 
-Page 54 of 88- 

for exceedances to occur. Therefore, the likelihood of adverse effects to fish, aquatic 

invertebrates, and aquatic-phase amphibians, from exposure to bicyclopyrone from the proposed 

uses is considered low. Estuarine/marine invertebrates are more sensitive than freshwater 

invertebrates on an acute exposure basis. However, based on chronic toxicity values estimated 

using ACRs, RQ values are below the chronic risk LOC for estuarine/marine fish and 

invertebrates. 

The risk hypothesis and conceptual diagrams articulated in the initial problem formulation of this 

assessment identified concerns that the proposed use of bicyclopyrone may result in adverse 

effects on survival and growth in aquatic plants, and chronic risk to small (15 g) and medium (35 

g) size classes of mammals. Data indicate monocots are less susceptible to the toxic effects of 

bicyclopyrone than are dicots. RQ values for non-listed dicots in semi-aquatic areas exceed the 

Agency’s LOC for risk to plants. RQ values for listed dicots exceed the Agency’s LOC for 

plants in dry and semi-aquatic areas due to exposure from runoff and spray drift combined, as 

well as for exposure from spray drift alone. Submitted bicyclopyrone data could not be used to 

determine chronic risk to avian taxa (and terrestrial-phase amphibians and reptiles) as 

reproductive effects were observed at all test concentrations used in the studies thereby not 

establishing a NOAEL. Additionally, the acute study with the passerine species resulted in 

regurgitation and/or mortality. Therefore, risk to these taxa cannot be precluded. Although the 

acute oral and contact terrestrial invertebrate studies indicate bicyclopyrone is practically nontoxic to the honey bee, there is uncertainty regarding the potential acute and chronic effects of 

the compound on honey bee larval development and survival as well as potential for chronic 

effects of adult bees. 

5. Federally Threatened and Endangered (Listed) Species of Concern 

Consistent with the Agency’s responsibility under the Endangered Species Act (ESA), the 

Agency evaluates risks to listed species from registered use of bicyclopyrone. This assessment is 

conducted in accordance with the Overview Document (USEPA, 2004), provisions of the 

Endangered Species Act (ESA), and the Services’ Endangered Species Consultation Handbook

(USFWS/NMFS, 1998). 

5.1. Action Area 

For listed species assessment purposes, the action area is considered to be the area affected 

directly or indirectly by bicyclopyrone use and not merely the immediate area where 

bicyclopyrone is applied. At the initial screening-level, the risk assessment considers broadlydescribed taxonomic groups and conservatively assumes that listed species within those broad 

groups are co-located with the pesticide treatment area. This means that terrestrial plants and 

wildlife are assumed to be located on or adjacent to the treated site, and aquatic organisms are 

assumed to be located in a surface water body adjacent to the treated site. The assessment also 

assumes that listed species are located within an assumed area which has the highest relative 

potential exposure to the pesticide, and that exposures are likely to decrease with distance from 

the treatment area. Section 6.2 of this risk assessment presents the proposed pesticide use sites 

that are used to establish initial co-location of species with treatment areas. 
-Page 55 of 88- 

5.2. Taxonomic Groups Potentially at Risk 

If the assumptions associated with the screening-level action area result in RQs that are below 

the listed species LOCs, a "no effect" determination conclusion is made with respect to listed 

species in that taxa, and no further refinement of the action area is necessary. Furthermore, RQs 

below the listed species LOCs for a given taxonomic group indicate no concern for indirect 

effects on listed species that depend upon the taxonomic group for which the RQ was calculated. 

However, in situations where the screening assumptions lead to RQs in excess of the listed 

species LOCs for a given taxonomic group, a potential for a "may affect" conclusion exists and 

may be associated with direct effects on listed species belonging to that taxonomic group or may 

extend to indirect effects upon listed species that depend upon that taxonomic group as a 

resource. In such cases, additional information on the biology of listed species, the locations of 

these species, and the locations of use sites could be considered to determine the extent to which 

screening assumptions regarding an action area apply to a particular listed organism. These 

subsequent refinement steps could consider how this information would impact the action area 

for a particular listed organism and may potentially include areas of exposure that are downwind 

and downstream of the pesticide use site. 

Assessment endpoints, exposure pathways, the conceptual diagram addressing the proposed new 

bicyclopyrone use, and the associated exposure and effects analyses conducted for the 

bicyclopyrone screening-level risk assessment are in Sections 2 to 3. The assessment endpoints 

used in the screening-level risk assessment include those defined operationally as reduced 

survival and reproductive impairment for both aquatic and terrestrial animal species and survival, 

reproduction, and growth of non-target aquatic and terrestrial plant species from exposure via 

spray drift and runoff. These assessment endpoints address the standard set forth in the 

Endangered Species Act requiring federal agencies to ensure that any action it authorizes does 

not appreciably reduce the likelihood of both the survival and recovery of a listed species in the 

wild by reducing the reproduction, numbers, or distribution of the species. Risk estimates (RQ 

values) integrating exposure and effects are calculated for broad-based taxonomic groups in the 

screening-level risk assessment and are presented in Section 4.

Both acute and chronic risk to listed species LOCs are considered in the screening-level risk 

assessment to identify direct and indirect effects to taxa of listed species. This section identifies 

direct and indirect effect concerns, by taxa, that are triggered by exceeding listed species LOCs 

in the screening-level risk assessment. Although concern levels were not exceeded for risk to 

fish, aquatic-phase amphibians, mollusks, invertebrates, birds, terrestrial-phase amphibians, and 

reptiles, indirect effects to these taxa are possible given the potential for adverse effects to 

terrestrial and semi-aquatic plants (via spray drift which cannot be precluded) and mammals. 

Potential effects include, but are not limited to, reduction in food resources, decrease in cover, 

change in water quality parameters, and loss of breeding/nesting habitat. Additional Description 

of Assumptions, Limitations, Uncertainties, Strengths and Data Gaps 
-Page 56 of 88- 

Aquatic Exposure 

This assessment is based upon available environmental fate data. There are no significant data 

gaps in the environmental fate database submitted by the registrant. However, there is some 

uncertainty introduced by a supplemental submitted non-guideline aerobic aquatic metabolism 

study that was irradiated during the incubation (MRID 47842075; water pH 7.5-7.9, sediment pH 

7.1-7.3). In the study, bicyclopyrone dissipated with half-lives of 7.4 and 7.5 days, despite the 

fact that the compound photodegrades only slowly in water, with respective half-lives of 11 and 

50 days at pH 5 and 7, and 74.8 days in natural water (pH 7.3), and was relatively stable in the 

submitted guideline aerobic aquatic studies (which are conducted in darkness). However, the 

significance of this (i.e., rapid dissipation when the study includes irradiation compared with 

relative stability when it is conducted in darkness) is unclear, and there were multiple issues with 

the study that resulted in a classification of “reliable with restrictions.” 

  

Additionally, the registrant has sought to show that parent compound transported below the soil 

surface may be wicked upward through evaporative transport flux in the soil and subsequently 

photodegraded on the surface soil, resulting in more rapid degradation than would occur in soil 

through metabolism alone (MRIDs 47842030, 47842170). The registrant has hypothesized that 

the rapid dissipation and lack of substantial leaching in the terrestrial field studies is attributable 

to this process. However, the correlation between half-lives and total irradiance is poor (with 

and without accounting for water input during the first week), and it is noted that the maximum 

concentration for the soil photolysis transformation product SYN503780 was observed at 1 day 

post-treatment in two of the three U.S. terrestrial field studies, and was not detected below the 0- 

to 15-cm depth in those. However, in prospective groundwater studies following parent 

bicyclopyrone application, SYN503780 was detected in wells at sampling intervals up to 3 years 

after application.

  

SWCC simulates the impact of daily weather on the treated agricultural field, and resulting 

concentrations in an adjacent farm pond over a defined period (here, thirty years). During this 

time, pesticide is washed-off of the field into the water-body by twenty to forty rainfall/runoff 

events per year. Each new addition of pesticide mass adds to the existing pesticide mass left over 

in the pond from previous runoff and/or spray-drift events. Since bicyclopyrone is persistent in 

aquatic environments, it accumulates in the pond from one year to the next. One consequence is 

that the yearly simulated peaks are not independent of year other but are temporally autocorrelated, meaning that the “1-in-10 year EECs” obtained from model post-processing are in 

part functions of the simulation duration, and are therefore inaccurate. As a result, SWCC results 

likely overestimate concentrations in streams and various other kinds of water bodies, as over the 

course of thirty years, some loss of bicyclopyrone is expected due to washout, dispersion, burial 

of sediment and other dissipative processes that aren’t simulated. In particular, bicyclopyrone 

concentrations in lotic (flowing) water bodies are not expected to accumulate from year to year 

because of downstream advective removal.

  

The labels specify that bicyclopyrone is generally to be applied once annually; however, a split 

application for pre-emergent and early post-emergent is allowed, provided the maximum 

recommended application/year of 0.04 lb a.i./A (50g/ha). Aquatic exposure in this assessment is 
-Page 57 of 88- 

based on the single pre-emergent application. If a split application is used, the acute aquatic 

exposure in the environment may be less than that estimated quantitatively in this assessment. 

For ecological effects, no data have been submitted for chronic effects to estuarine/marine fish 

and invertebrates. However, ACRs were used to estimate chronic toxicity values for both the 

estuarine/marine fish and invertebrates 

Terrestrial Exposure 

Bicyclopyrone is generally applied once annually; however, a split application for pre-emergent 

and early post-emergent is allowed, provided the maximum recommended application/year of 

0.04 lb a.i./A (50g/ha). Terrestrial exposure in this assessment is based on a single application. 

Also, if applied as a pre-emergent, bicyclopyrone will be applied to the soil surface rather than 

on growing plants. Thus, actual terrestrial exposure in the environment may be less than that 

estimated quantitatively in this assessment. 

There is uncertainty with the avian reproduction studies due to the lack of dose-response in both 

studies. Specifically, for the bobwhite quail study, a dose-response was not observed for mean 

hatching weight even though a statistically significant effect was detected. In the mallard study, 

a dose-response was not observed for eggs laid/hen and mean 14-day old survivors weight even 

though a statistically significant effect was observed across multiple dietary treatment levels. 

Although mean hatchling weight appeared to be somewhat treatment-related, the highest 

bicyclopyrone dietary concentration showed the lowest difference compared to controls while 

the lowest bicyclopyrone dietary concentration had the greatest difference. In both avian 

reproduction studies there appeared to be considerable variability in control birds making it 

difficult to detect treatment effects. However, using the most conservative bicyclopyrone 

toxicity value (i.e., mallard NOAEL of 35 mg ai/kg diet) in risk estimation, no chronic risk LOC 

is exceeded. In order for chronic exceedances to occur, the toxicity value for the Mallard study 

would have to be 10 mg ai/kg diet based on an application rate on corn of 0.045 lbs ai/A with 1 

application. 

Table 5.1. Potential effects to federally listed avian taxa associated with the proposed used of TGAI 

bicyclopyrone. 

Mallard duck 

(Anas platyrhynchos) 

MRID 47842084 

Corn 0.045 lbs a.i./A; 1 application 

Dietary Category Chronic RQs 

Short Grass 0.29 

Tall Grass 0.13 

Broadleaf plants 0.16 

Fruits/pods/seeds 0.02 

Arthropods 0.11 

Granivore NA 

 NA=Not applicable 

 1 Chronic risk LOC exceeded for listed and non-listed species is 1.0. 
-Page 58 of 88- 

The submitted acute oral toxicity study to a passerine species (MRID 47842078) is classified as 

supplemental because exposed canaries exhibited regurgitation and mortality was observed at 

multiple test concentrations. 

Although data from the acute contact and oral toxicity tests with young adult honey bees indicate 

bicyclopyrone is practically non-toxic to bees on an acute exposure basis, there is uncertainty 

regarding the potential acute and chronic effects of the compound on honey bee larval 

development and survival as well as potential for chronic effects of adult bees. Since 

bicyclopyrone is a systemic herbicide, residues may be transported to pollen and/or nectar and 

represent a route of exposure for bees through both contact and ingestion. Therefore, additional 

data on pollinators are needed to fully characterize the potential risk associated with 

bicyclopyrone use to all developmental stages of honey bees, as sensitivity may vary according 

to life-stage and length of exposure (adult vs. larval and acute vs. chronic, respectively). 

Data Gaps 

There are no fate data gaps for bicyclopyrone. 

Appendix F lists whether data gaps for ecological effects have been identified. 

No data have been submitted for chronic toxicity to estuarine/marine fish and invertebrates. 

Therefore, estuarine/marine invertebrate life-cycle (OCSPP 850.1350) and estuarine/marine fish 

early-life stage (OCSPP 850.1400) are classified as data gaps. However, in the absence of these 

data, ACRs have been used to estimate chronic toxicity endpoints for these taxa. 

The submitted acute oral toxicity study to a passerine species (MRID 47842078) is classified as 

supplemental because regurgitation and mortality coincided at multiple test concentrations to 

exposed canaries. Furthermore, the study resulted in a more sensitive endpoint than the other 

acute avian studies submitted and thus would be important in the characterization to avian taxa. 

Therefore this study is listed as a data gap. 

6. References 

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(Kenaga) nomogram, and instrument for estimating pesticide residues on plants. Environmental 

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Hoerger, F., and E.E. Kenaga. 1972. Pesticide residue s on plants: Correlation of representative data as a basis for 

estimation of their magnitude in the environment. In F. Coulston and F. Korte, eds., Environmental Quality 

and Safety: Chemistry, Toxicology, and Technology, Georg Thieme Publ, Stuttgart, West Germany, pp. 9-

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USEPA. 2014a. Data on Bicyclopyrone and Its Environmental Transformation Products in Support of the ROCKS. 

September 2014 Memo from Ideliz Negrón-Encarnación, ROCKS Alternate Secretary Health Effects 

Division, to Bicyclopyrone Risk Assessment Team Risk Assessment Branch I, HED. DP Barcode 

D421264. 
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USEPA. 2014b. Bicyclopyrone. Report of the Residues of Concern Knowledgebase Subcommittee (ROCKS). July 

24, 2014 Memo from Cheryl Sutton and Andrew Sayer, EFED, to ROCKS Co-Chairs Christine Olinger, 

HED, and Edward Scollon, EFED. DP Barcode D421260. 

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September 11, 2012. U.S. Environmental Protection Agency. Pest Management Regulatory Agency. 

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http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2012-0543-0004 (Accessed August 18, 

2014). 

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Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs, Washington, D.C. Available 

online at http://www.epa.gov/oppfead1/endanger/consultation/ecorisk-overview.pdf

USEPA. 1998. Guidelines for Ecological Risk Assessment. EPA/630/R-95/002F. Published in 63 FR 26846; May 

14, 1998. U.S. Environmental Protection Agency, Washington, DC. April, 1998. Available at 

http://www.epa.gov/raf/publications/pdfs/ECOTXTBX.PDF 

USFWS/NMFS. 1998. Endangered Species Consultation Handbook: Procedures for Conducting Consultation and 

Conference Activities Under Section 7 of the Endangered Species Act. Final Draft. United States Fish and 

Wildlife Service (USFWS) and National Marine Fisheries Service (NMFS). Available at 

http://sero.nmfs.noaa.gov/pr/esa/pdf/Sec%207%20Handbook.pdf (Accessed November 7, 2012). 

 

Fate MRIDs 

MRID 47841919. Adam, D., 2008. [Pyridinyl-14C]-labelled NOA449280 – Hydrolysis at four different pH values. 

Syngenta Ltd., Jealott’s Hill International Research Centre, Bracknell, Berkshire, RG42 6EY, UK. RCC Study 

Number: B75598. Syngenta Sypos task ID: T013175-05. 

MRID 47842075. Adam, D., 2010. NOA449280 – Route and rate of degradation in water/sediment system under 

artificial sunlight. Syngenta Ltd., Jealott’s Hill International Research Centre, Bracknell, Berkshire, RG42 6EY, UK. 

Study Number: 115 01 042. Task Number: T002567-08. 

MRID 47842055. Brice, A.; Gilbert, J. 2010. NOA449280- Adsorption and Desorption Properties in Seven Soils: 

Final Report. Project Number: 1'001923/07/0C~ 1983/076/D2149, 1983/076. Unpublished study prepared by 

Covance Laboratories, Ltd. 144 p. 

MRID 47842027. Brice A and J. Gilbert, 2010. NOA449280 - Metabolism and rate of degradation of 14C-pyridinyl 

and 14C-bicyclooctenone labelled NOA449280 under anaerobic laboratory conditions, in one Soil, at 20°. Syngenta 

Ltd., Jealott’s Hill International Research Centre, Bracknell, Berkshire, RG42 6EY, UK. Report Number: 1983/070-

D2149. Task Number: T013196-05. 

MRID 47842066. Finger, N., 2012a. NOA449280 - Leaching behaviour of NOA449280 and its metabolite into 

groundwater in a field trial – Lorsch, Germany, 2007-2012. Syngenta Ltd., Jealott’s Hill International Research 

Centre, Bracknell, Berkshire, RG42 6EY, UK. Report Number: S07-00066-Interim-1. Task Number: TK0009218. 

MRID 47842067. Finger, N., 2012b. NOA449280 - Leaching behaviour of NOA449280 and its metabolite into 

groundwater in a field trial – Aba, Hungary. Syngenta Ltd., Jealott’s Hill International Research Centre, Bracknell, 

Berkshire, RG42 6EY, UK. Report Number: S08-01322-Interim-1. Task Number: TK0009273. 

MRID 47842068. Finger, N., 2012c. NOA449280 - Leaching behaviour of NOA449280 and its metabolite into 

groundwater in a field trial – Alsace, France. Syngenta Ltd., Jealott’s Hill International Research Centre, Bracknell, 

Berkshire, RG42 6EY, UK. Report Number: S08-01327-INTERIM-1. Task Number: TK0009274. 
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MRID 47842073. Gassen M, 2009, NOA449280 - [Pyridinyl-3-14C]-labelled NOA449280 - Metabolism and rate of 

degradation under aerobic and anaerobic conditions in aquatic systems. Syngenta Ltd., Jealott’s Hill International 

Research Centre, Bracknell, Berkshire, RG42 6EY, UK. Study Number: B44425. Syngenta Reference Number: 

T013193-05. 

MRID 47842074. Gassen M, 2010. [Bicyclooctenone-6,7-14C2]-labelled NOA449280 – Metabolism and rate of 

degradation under aerobic and anaerobic conditions in aquatic systems. Syngenta Ltd., Jealott’s Hill International 

Research Centre, Bracknell, Berkshire, RG42 6EY, UK. Study Number: B46012. Syngenta Reference Number: 

T013194-05. 

MRID 47842030. Hand, L., C. Nichols and S. Kuet, 2012.Investigation into the factors controlling photolysis and 

the movement of the active ingredient within soil. Syngenta Ltd., Jealott’s Hill International Research Centre, 

Bracknell, Berkshire, RG42 6EY, UK. Report Number: PM-08-533. Task Number: T000808-07. 

MRID 47842026. Lewis C., 2009. NOA449280 – Metabolism and Rate of Degradation of 14C-Bicyclooctenone 

Labelled NOA449280 under Aerobic Laboratory Conditions, in One Soil, at 20°C, Covance Laboratories Limited, 

UK. Report Number: 1983/071-D2149. Unpublished report (Syngenta File No. NOA449280_11046). 

MRID 47842026. Lewis, C.; Gilbert, J. 2012. NOA449280- Metabolism and Rate of Degradation of [Carbon 

14]Bicyclooctenone Labelled NOA449280 Under Aerobic Laboratory Conditions, in One Soil, at 20 (Degrees 

Celsius): Final Report. Project Number: T013183/05/0CR, 1983/071/D2149, 

1983/071. Unpublished study prepared by Covance Laboratories, Ltd. 83 p. 

MRID 47842032. Brice, A.; Heslop, D. 2009. NOA449280 - Rate of Degradation ofNOA449280 Under Aerobic 

Laboratory Conditions, in Five Soils, at 20 (Degrees Celsius): Final Report. Project Number: 

T001436/08/0CR, 1983/089/D2149. Unpublished study prepared by: Covance Laboratories, Ltd .. 

117p. 

MRID 47842033. Lewis, C.; Gilbert, J. 2009. NOA449280 - Metabolism and Rate of Degradation of [Carbon 

14]Pyridine Labelled NOA449280 Under Aerobic Laboratory Conditions, in Seven US Soils, at 20 (Degrees 

Celsius): Final Report. Project Number: T001922/07/0CR, 1983/075/D2149. 

Unpublished study prepared by Covance Laboratories, Ltd. 222 p. 

 MRID 47842034. Lewis, C.; Gilbert, J. 2009. NOA449280- Metabolism and Rate of Degradation of [Carbon 

14]Pymine Labelled NOA449280 Under Aerobic Laboratory Conditions, in Five Soils, at 20 (Degrees Celsius): 

Final Report. Project Number: T013182/05/0CR, 1983/069/D2149. Unpublished study 

prepared by: Covance Laboratories, Ltd . 188 p. 

MRID 47842036. Lewis, C.; Gilbert, J. 2010. NOA449280- Rate of Degradation of [Carbon 14]-Pyridine Labelled 

SYN503780, a Soil Metabolite, Under Aerobic Laboratory Conditions, in Three Soils, at 20 (Degrees Celsius). 

Project Number: T005859/06/0CR, 1983/085/D2149. Unpublished study 

prepared by: Covance Laboratories, Ltd. 170 p. 

MRID 47842037. Dixon, K.; Gilbert, J. 2010. NOA449280- Rate of Degradation of [Carbon 14]-Pyridine Labeled 

CSAA806573, a Soil Metabolite, Under Aerobic Laboratory Conditions, in Three Soils, at 20 (Degrees Celsius): 

Final Report. Project Number: T007596/08/0CR, 1983/113/D2149. 

Unpublished study prepared by Covance Laboratories, Ltd. 117 p. 

MRID 47841921. Lewis C. J. And J. Gilbert, 2009. [14C]NOA449280 - Photodegradation and quantum yield in 

sterile, aqueous solution. Syngenta Ltd., Jealott’s Hill International Research Centre, Bracknell, Berkshire, RG42 

6EY, UK. Report Number: 8215834-D2149, Task Number: TK011883. 

MRID 47842028. Lewis, C.J. and J. Gilbert, 2010. [14C]NOA449280 - Photodegradation on Soil Surface. Final 

Report Amendment 1.Syngenta Ltd., Jealott’s Hill International Research Centre, Bracknell, Berkshire, RG42 6EY, 

UK. Report Number: 1983/072-D2149, Task Number: T013191-05. 
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MRID 47842029. Lewis, C.J. and J. Gilbert, 2011. [14C]NOA449280 -Photodegradation on three US soils. 

Syngenta Ltd., Jealott’s Hill International Research Centre, Bracknell, Berkshire, RG42 6EY, UK. Report Number: 

8215834-D2149, Task Number: TK011883. 

MRID 47842060 Lewis, C.; Gilbert, J. 2009. NOA449280- Adsorption and Desorption Properties of 

[Carbon14]SYN503780 in Four Soils: Final Report. Project Number: 1'005863/06/0CR, 1983/086/D2149. 

Unpublished study prepared by Covance Laboratories, Ltd. 72 p. 

MRID 47842057 Lowden, P.; Brett, R. 2009. [Carbon 14]-NOA449280- Adsorption and Desorption Properties of 

Two Soils: Final Report. Project Number: 1'013198/05/0CR, NC/07/003. Unpublished study 

prepared by Battelle UK Ltd. 85 p. 

MRID 47841909. Geoffroy, A., 2007. NOA449280 – Vapour Pressure. Syngenta Crop Protection Münchwilen AG, 

CH-4333 Müchhwilen, Switzerland. Study Number: L07-002662. 

MRID 47841914. Weissenfeld, M., 2009. NOA449280 Determination of the water solubility. Syngenta Crop 

Protection Münchwilen AG, Breitenloh 5, 4333 Münchwilen, Switzerland. Harlan Laboratories Study B46056. 

MRID 47842060. Peranginangin, N., D.P. Simmons, A. Sapiets, C. Nichols, 2012. Refined modelling of 

NOA449280 using data from targeted higher tier laboratory studies to reflect a conceptual model of dissipation 

pathways under field conditions. Syngenta Crop Protection, LLC., Greensboro, NC. Report Number: TK0009393. 

MRID 47842038. Simmons, D. and A. Newcombe, 2011a. Dissipation of NOA449280 EC Formulation in Bare Soil 

Plots Under Simulated Field Corn Production Conditions. Syngenta Crop Protection , LLC., Greensboro, NC. 

Report Number: T004878-06. 

MRID 47842039. Simmons, D., B. Jacobson, N. McLean and A. Sapiets, 2011a. Dissipation of NOA449280 EC 

formulation on bare soil under simulated corn production conditions in Iowa. Syngenta Crop Protection, LLC., 

Greensboro, NC. Report Number: T004878-06. 

MRID 47842040. Simmons, D., B. Jacobson, N. McLean and A. Sapiets, 2011b. Dissipation of NOA449280 EC 

formulation on bare soil under simulated corn production conditions in Nebraska. Syngenta Crop Protection, LLC., 

Greensboro, NC. Report Number: T004880-06. 

MRID 47842070 S:immns, D.; McLean, N. 2012. NOA449280- Stability of NOA449280 and SYN503780 in Soil 

Under Freezer Storage Conditions: Final Report. Project Number: T002698/07/ORC, 

11SYN2791REP. Unpublished study prepared by Syngenta Crop Protection LLC and ALS Environmental 141 p. 

MRID 47842162. Simmons, D.; McLean, N. 2012. StabilityofCSCC163768, CSCD656832, CSCD642512 and 

CSAA806573 in Soil Under Freezer Storage Conditions: Final Report. Project Number: T013395/05/0C~ 

12SYN3161REP. Unpublished study prepared by Syngenta Crop Protection, 

LLC and ALS Environmental 267 p. 

MRID 47842069. Trevisan, M., 2012. NOA449280 – Field leaching behaviour study at site L01 (Orzinuovi-BS) in 

Italy – multisite study. Syngenta Ltd., Jealott’s Hill International Research Centre, Bracknell, Berkshire, RG42 6EY, 

UK. Report Number: CZ/08/019/UCSC/NOAGL1/R1. Task Number: TK002356-07 (TK0009355). 

MRID 47842071. Zietz, E., 2012. NOA449280 - Leaching behaviour of NOA449280 and its metabolite 

SYN503780 into groundwater in a field trial – Buzet-sur-Tarn, France. Syngenta Ltd., Jealott’s Hill International 

Research Centre, Bracknell, Berkshire, RG42 6EY, UK. Report Number: IF-08/01121619-INT-1. Task Number: 

TK002355-07. 

MRID 47842123. Zietz, E. 20 12. NOA449280 - Determination of the Storage Stability ofNOA449280 and its 

Metabolites SYN503780, CSCC163768, CSCD656832, CSCD642512 and CSAA806573 in 

Groundwater: Final Report. Project Number: TK0009215/0CR, IF/09/01378891. Unpublished 
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study prepared by SGS Institut Fresenius GmbH. 97 p. 

MRID 47842117. Brain, R. 2011. NOA449280- Waiver Justification for Fish Bioaccumulation Study. Project 

Number: TK0089334/0CR Unpublished study prepared by Syngenta Crop Protection, LLC. 5 p 

MRID 47841950. Braid, S.; McLean, N. (2009) NOA449280- Residue Analytical Method fur the Determination of 

NOA449280 and its Metabolites SYN503780, CSCD656832, CSCD642512, CSCC163768 and CSAA806573 in 

Soil Final Determination by LC-MS/MS. Project Number: 1'000993/08/0CR, GRM030/04A. Unpublished study 

prepared by Syngenta Jealotts Hill International Research Centre. 144p. 

MRID 47841954 Crook, S. (2008) NOA449280- Residue Method for the DeterminationofNOA449280 and 

Metabolite SYN503780 in Water: Final Determination byLC-MS/MS. Project Number: 

T010139/040CR, GRM030/01A. Unpublished study prepared by Syngenta Jealotts Hill 

International Research Centre. 48 p. 

MRID 47841955 Morriss, A; Eversfield, S. (2008) NOA449280- Validation of a Method (Draft GRM030.01A) for 

the DeterminationofNOA449280 and SYN503780 in Drinking, Surface and Ground Water. Project Number: 

1'013212/05/0CR, CEMR/3547. Unpublished study prepared by CEM Analytical 

Services, Ltd. 35 p. 

MRID 47841956 Zietz, E. (2011) NOA449280- Validation of an Analytical Method (Draft GRM030.06A) for the 

DeterminationofNOA449280 and its Metabolites SYN503780, CSCC163768, CSCD656832, 

CSCD642512 and CSAA806573 in Water. Project Number: TK0009384/0CR, lF/09/01378742. 

Unpublished study prepared by SGS Institut Fresenius Chemische und Biologische. 123 p. 

MRID 47841959. Oppilliart, S. (2008) NOA449280-Validation of Residue Method AGRIMOA/NOA449280-2 for 

the DeterminationofNOA449280 in Air: Final Report. Project Number: 1'013551/05/0CR, 1'013551/05/REG. 

Unpublished study prepared by ADME Bioanalyses. 41 p. 

MRID 47841949. Hargreaves, S. (2007) NOA449280 - Residue Method fur the Determination ofNOA449280 and 

Metabolite SYN503780 in Soil: Analytical Method. Project Number: T013208/05/0CR,GRM/030/02A. 

Unpublished study prepared by Syngenta Jea1otts Hill International Research Centre. 47 p. 

MRID 47841950. Braid, S.; McLean, N. (2009) NOA449280 - Residue Analytical Method fur the Determination of 

NOA449280 and its Metabolites SYN503780, CSCD656832, CSCD642512, CSCC163768 and CSAA806573 in 

Soil Final Determination by LC-MS/MS. Project Number: 1'000993/08/0CR, GRM030/04A. Unpublished study 

prepared by Syngenta Jea1otts Hill International Research Centre. 144p. 

MRID 47841951. Eversfield, S. (2007) Va1idation of a Method (Draft GRM030.02A) for the Determination of 

NOA449280 and SYN503780 in Soil Project Number: 1'013392/05/0CR, CEMR/3644. 

Unpublished study prepared by CEM Analytical Services, Ltd. 31 p. 

MRID 47841952. Hagan, M. (2009) NOA449280 - Validation of Draft Method GRM030.04A for the Determination 

of NOA449280, SYN503780, CSCC163768, CSCD656832, CSCD642512 and CSAA806573 in Soil: Final Report. 

Project Number: T001384/09, 09SYN256/REP, ALS09SYN01/PRO. Unpublished study prepared by ALS 

Laboratory Group, Environmental. 109 p. 

MRID 47841953 Oppilliart, S. (2009) NOA449280 - Validation of Analytical Method GRM030.04A for the 

Determination of Residues ofNOA449280 and Metabolites SYN503780, CSCD656832, CSCD642512, 

CSCC163768 and CSAA806573 in Soil Project Number: TK0014608/0CR, TK0014608/REG, S09/02700. 

Unpublished study prepared by ADME Bioanalyses. 163 p. 

Ecological Effects MRIDs 
-Page 63 of 88- 

MRID 47842079. Hubbard PM and Beavers JB (2009), NOA449280: An acute oral toxicity study with the Northern 

Bobwhite. Laboratory Report Number 528-305. Wildlife International Ltd, Easton, Maryland, USA, 2009. 

Unpublished report. (Syngenta File No. NOA449280_11015). 

MRID 47842080. Hubbard P.M., Martin K.H. & Beavers J.B. (2007). NOA449280 – A dietary LC50 study with the 

Northern Bobwhite. Laboratory Report Number 528-249. Wildlife International Ltd, Easton, Maryland, USA. 

Unpublished report. (Syngenta File No. NOA449280/0077). 

MRID 47842081. Hubbard P.M., Martin K.H. & Beavers, J.B. (2007a). NOA449280 – A dietary LC50 study with 

the Mallard. Laboratory Report Number 528-250. Wildlife International Ltd, Easton, Maryland, USA. Unpublished 

report. (Syngenta File No. NOA449280/0078). 

MRID 47842082. Frey, L.T., Martin K.H., Beavers, J.B. & Jaber, M. (2008). NOA449280 – A reproduction study 

with the Northern Bobwhite. Laboratory Report Number 528-253. Wildlife International Ltd, Easton, Maryland, 

USA. Unpublished report. (Syngenta File No. NOA449280_10995). 

MRID 47842084. Frey, L.T., Martin K.H., Beavers, J.B. & Jaber, M. (2009). NOA449280 – A reproduction study 

with the Mallard. Laboratory Report Number 528-289. Wildlife International Ltd, Easton, Maryland, USA. 

Unpublished report. (Syngenta File No. NOA4449280_11034). 

MRID no. 47842085. Bätscher, R. (2007). NOA449280 - Acute toxicity to rainbow trout (Oncorhynchus mykiss) in 

a 96-hour static test. Laboratory Report Number B37091. RCC Ltd, Itingen, Switzerland. Unpublished report. 

(Syngenta File No. NOA449280/0087). 

MRID no. 47842086. Bätscher, R. (2007a). NOA449280 - Acute toxicity to fathead minnow (Pimephales 

promelas) in a 96-hour static test. Laboratory Report Number B37135. RCC Ltd, Itingen, Switzerland. Unpublished 

report. (Syngenta File No. NOA449280/0084). 

MRID no. 47842087. Gallagher, S. P., Kendall, T. Z., and H. O. Krueger (2008). NOA449280: An early life stage 

toxicity test with the fathead minnow (Pimephales promelas). Laboratory Report Number 528A-167. Wildlife 

International Ltd., Easton, MD, USA. Unpublished report. (Syngenta File No. NOA449280/0102). 

MRID no. 47842088. Bätscher, R. (2007b), NOA449280 - Acute toxicity to Daphnia magna in a 48-hour 

immobilization test. Laboratory Report number B37056. RCC Ltd, Itingen, Switzerland. Unpublished report. 

(Syngenta File No. NOA449280/0083). 

MRID no. 47842091. Bätscher, R. (2008). NOA449280 - Effect on survival, growth and reproduction of Daphnia 

magna in a semi-static test over three weeks. Laboratory Report number B37078. RCC Ltd, Itingen, Switzerland. 

Unpublished report. (Syngenta File No. NOA449280/0092). 

MRID no. 47842092. Bätscher, R. (2007c). NOA449280 - Toxicity to Pseudokirchneriella subcapitata (formerly 

Selenastrum capricornutum) in a 96-hour algal growth inhibition test. Laboratory Report Number B36977. RCC 

Ltd, Itingen, Switzerland. Unpublished report. (Syngenta File No. NOA449280/0081). 

MRID no. 47842093. Büche, C. (2008). NOA449280 - Toxicity to Anabaena flos-aquae in a 96 hour algal growth 

inhibition test. Laboratory Report Number B36990. RCC Ltd, Itingen, Switzerland. Unpublished report. (Syngenta 

File No. NOA449280/0082). 

MRID no. 47842094. Büche, C. (2007). NOA449280 - Toxicity to Navicula pelliculosa in a 96 hour algal growth 

inhibition test. Laboratory Report Number B37012. RCC Ltd, Itingen, Switzerland. Unpublished report. (Syngenta 

File No. NOA449280/0085). 

MRID no. 47842102. Minderhout, T., Kendall, T. Z., and H. O. Krueger. (2008). NOA449280: A 96-hour toxicity 

test with the marine diatom (Skeletonema costatum). Laboratory Report Number 528A-161. Wildlife International, 

Ltd., Easton, Maryland, USA. Unpublished report. (Syngenta File No. NOA449280/0093). 
-Page 64 of 88- 

MRID no. 47842095. Bätscher, R. (2007d). NOA449280 - Toxicity to the Aquatic Higher Plant Lemna gibba in a 

7-Day Semi-Static Growth Inhibition Test. Laboratory Report Number B37034. RCC Ltd. Zelgliweg 1, 4452 

Itingen, Switzerland. Unpublished report. (Syngenta file No. NOA449280/0071). 

MRID no. 47842116. Peither, A. (2011). NOA449280 EC (A15749AD) - Toxicity to the aquatic higher plant 

Lemna gibba in a 7-day growth inhibition test, supplemented with testing for recovery of growth. Laboratory 

Report Number B95095. Harlan Laboratories Ltd., 4452 Itingen, Switzerland. Unpublished report. (Syngenta file 

no. A15749AD_10016). 

MRID no. 47842096. IIA 8.7.1/01. Warmers, C. (2007): NOA449280 - Acute Oral and Contact Toxicity to the 

Honeybee Apis mellifera L. in the Laboratory. Laboratory Report Number 20071298/01-BLEU. Eurofins-GAB 

GmbH, Niefern-Öschelbronn, Germany. Unpublished report. (Syngenta file No. NOA449280/0065). 

MRID no. 47842097. Stevens, J. (2009). NOA449280 EC (A15749AD) – A rate-response laboratory bioassay of 

the effects of fresh residues on the parasitic wasp Aphidius rhopalosiphi (Hymenoptera, Braconidae). Laboratory 

Report Number SYN-08-46. Mambo-Tox Ltd., 2 Venture Road, Chilworth Science Park, Southampton SO16 7NP, 

UK. Unpublished report. (Syngenta file No. A15749AD_10002). 

MRID no. 47842118. Fallowfield, L. (2009). NOA449280 EC (A15749AD) – A rate-response laboratory bioassay 

of the effects of fresh residues on the predatory mite, Typhlodromus pyri (Acari: Phytoseiidae). Laboratory Report 

Number SYN-08-45. Mambo-Tox Ltd., 2 Venture Road, Chilworth Science Park, Southampton SO16 7NP, UK. 

Unpublished report. (Syngenta file No. A15749AD_10003). 

MRID no. 47842150. Stevens, J, (2009a). NOA449280/S-metolachlor EC (A15936Z) – A rate response extended 

laboratory bioassay of the effects of fresh residues on the parasitic wasp Aphidius rhopalosiphi (Hymenoptera, 

Braconidae). Laboratory Report Number SYN-08-48. Mambo-Tox Ltd., 2 Venture Road, Chilworth Science Park, 

Southampton SO16 7NP, UK. Unpublished report. (Syngenta file No. A15936Z_10004). 

MRID no. 47842098. Friedrich, S. (2008), NOA449280 - Acute toxicity to the earthworm Eisenia fetida. 

Laboratory Report Number 07 10 48 035 S. BioChem agrar GmbH, Kupferstraße 6, D-04827 Gerichshain, 

Germany. Unpublished report. (Syngenta file No. NOA449280/0080). PMRA no. 2263386. 

MRID no. 47842099. Schulz, L. (2009), NOA449280 SL (A16003E) - Effects on the activity of soil microflora 

(Nitrogen and carbon transformation tests). Laboratory Report Number 09 10 48 023 C/N. BioChem agrar, 04827 

Gerichshain, Germany. Unpublished report. (Syngenta File No. A16003E_10002). 

MRID no. 47842101. Gallagher, S., Kendall, T. and H. Krueger. (2008a). NOA449280 – A 96 Hour Static Acute 

Toxicity Test with the Sheepshead Minnow (Cyprinodon variegatus). Laboratory Report Number 528A-159. 

Wildlife International Ltd, Easton, MD, USA. Unpublished report. (Syngenta File No. NOA449280/0101). 

MRID no. 47842089. Gallagher, S., Kendall, T. and H. Krueger. (2008b). NOA449280 – A 96 hour static acute 

toxicity test with the saltwater mysid (Mysidopsis bahia). Laboratory Report Number 528A-158. Wildlife 

International Ltd, Easton, MD, USA. Unpublished report. (Syngenta File No. NOA449280/0095). 

MRID no. 47842090. Gallagher, S., Kendall, T. and H. Krueger. (2008c). NOA449280 - A 96 hour shell deposition 

test with the eastern oyster (Crassostrea virginica). Laboratory Report Number 528A-160. Wildlife International 

Ltd, Easton, MD, USA. Unpublished report. (Syngenta File No. NOA449280/0096). 

MRID no. 47842103. Porch, J. R., Martin, K. H. & H. O. Krueger. (2009). NOA449280 EC (A15749F) - Toxicity 

Effects on the Seedling Emergence of Terrestrial Non-Target Plant Species. Laboratory Report No: 528-265. 

Wildlife International Ltd., Easton, MD 21601, USA. Unpublished report. (Syngenta file No. A15749F_10001). 

MRID no. 47842104. Porch, J. R., Martin, K. H. & H. O. Krueger. (2009a). NOA449280 EC (A15749F) - Toxicity 

Effects on the Vegetative Vigour of Terrestrial Non-Target Plant Species. Laboratory Report No: 528-266, Wildlife 

International Ltd., Easton, MD 21601, USA. Unpublished report. (Syngenta file No. A15749F_10002). 
-Page 65 of 88- 

MRID no. 47842105. Seyfried, B. (2007). NOA449280 - Toxicity to activated sludge in a respiration inhibition test. 

Laboratory Report number B37157. RCC Ltd, Itingen, Switzerland. Unpublished report. (Syngenta File No. 

NOA449280/0088). 

MRID no. 47842144. Rudolf R (2009). Screening Test for Acute Toxicity of CA3276A to Rainbow Trout

(Onchorynchus mykiss) (96-hour exposure without feeding): Laboratory Report Number TK00480-09, 50513261. 

IBACON Institut für Biologische Analytik und Consuting IBACON GmbH. Unpublished report. (Syngenta file no. 

CA3276A_11271). PMRA no. 2263484. 

MRID no. 47842145. Rudolf R (2009). Screening Test for Acute Toxicity of CA3276A to Daphnia magna Stauss 

(48 hours exposure without feeding): Laboratory Report Number TK00480-09, 50512262. IBACON Institut für 

Biologische Analytik zund Consuting IBACON GmbH. Unpublished report. (Syngenta file no. CA3276A_11270). 

MRID no. 47842146. Rudolf R (2009). Screening Test for Toxicity of CA3276A: A 72-hour algal growth 

inhibition test with Pseudokirchneriella subcapitata (formerly Selanastrum capricornutum) Laboratory Report 

Number TK00480-09, 50511260. IBACON Institut für Biologische Analytik zund Consuting IBACON GmbH. 

Unpublished report. (Syngenta file no. CA3276A_11272). 

MRID no. 47842147. Höger S (2009). Screening Test for Toxicity of CSAA794198 to Lemna gibba. Laboratory 

Report Number TK0009423. Harlan Laboratories Ltd Zelgliweg 1 4452 Itingen I Switzerland. Unpublished report. 

(Syngenta file no. NOA449280_11043). 

MRID no. 47842149. Höger S (2009). CSAA589691 - Toxicity to the Aquatic Higher Plant Lemna gibba in a 7-

Day Growth Inhibition Test. Laboratory Report Number C65658. Harlan Laboratories Ltd.Zelgliweg 1 4452 Itingen 

/ Switzerland. Unpublished report. (Syngenta file no. NOA412101_11214). 

MRID no. 47842139. Höger S (2010). CSCC163768 - Toxicity to the Aquatic Higher Plant Lemna gibba in a 7-

Day Growth Inhibition Test. Laboratory Report Number C62036. Harlan Laboratories Ltd.Zelgliweg 1 4452 Itingen 

/ Switzerland. Unpublished report. (Syngenta file no. SYN504810_10001). 

MRID no. 47842106. Boonstra, H., van Wijngaarden, R.P.A. and T.C.M. Brock (2010). NOA449280 – Outdoor 

Multi-Species Test with Aquatic Macrophytes. Laboratory Report Number ALT.HB.2008.1. ALTERRA, 

Wageningen University and Research Centre, Centre for Water and Climate, Wageningen, The Netherlands. 

Unpublished report. (Syngenta file no. NOA449280_11116). 

MRID no. 47842121. Nair, S.K. (2012). Development of 84-Day Multi-Species Exposure Response Curves for 

NOA449280. Laboratory Report Number: E2-SYN1293-2012-01. E2 Consulting Engineers, Inc., Oak Ridge, TN 

37830 USA. Unpublished report. (Syngenta file no. NOA449280_11147). 

MRID no. 47842248. Kling, A. 2009. NOA449280 SL (A16003E)- Acute oral and contact toxicity to the honeybee 

Apis mellifera L. in the laboratory. Final report. Performing lab: Eurofins-GAB GmbH, Germany. Report no. S09-

01234. Sponsor: Syngenta, UK. 

MRID no. 47842249. Friedrich, S. 2009. NOA449280 SL (A16003E) – Acute toxicity to the earthworm Eisenia 

fetida. Final report. Performing lab: BioChem agrar, Germany. Study number: 09 10 48 039 S. Sponsor: Syngenta, 

UK. 

MRID no. 47842242. Hoger, S. 2009. NOA449280 SL (200) (A16003E) – Acute toxicity to Daphnia magna in a 

48-hour immobilization test. Performing lab: Harlan Laboratories Ltd, Switzerland. Study no. C40932. Sponsor: 

Syngenta, UK. 

MRID no. 47842241. Hoger, S. 2009. NOA449280 SL (200) (A16003E) – Acute toxicity to rainbow trout 

(Oncorhynchus mykiss) in a 96-hour test. Final report. Performing lab: Harlan Laboratories Ltd., Switzerland. Study 

no. C40921. Sponsor: Syngenta, UK. 
-Page 66 of 88- 

MRID no. 47842250. Hubbard, P.M. and Beavers, J.B. 2009. NOA449280 EC (A16003E) – An acute oral toxicity 

study with the Northern Bobwhite using a sequential testing procedure. Final report. Performing lab: Wildlife 

International Ltd. Easton, MD. Report no. 528-295. Sponsor: Syngenta, UK. 

MRID no. 47842243. Hoger, S. 2009. NOA449280 SL (200) (A16003E) – Toxicity to Pseudokirchneriella 

subcapitata in a 96-hour algal growth inhibition test. Final report. Performing lab: Harlan Laboratories, Switzerland. 

Study no. C40908. Sponsor: Syngenta, UK. 
-Page 67 of 88- 

Appendix A. Proposed New Uses, Bicyclopyrone Proposed products for registration containing bicyclopyrone.

Proposed 

New End-Use 

Product Name 

Summary Formulation Details: 

Formulation Type 

lb bicyclopyrone/gal of product 

Application Type Crops 

SYN-A16003 

EPA Reg. No. 100-

RUAA 

Soluble concentrate (18.5% a.i.) 

1.67 Ground Corn (field corn, see

corn, yellow popcorn a

SYN-A19707; 

Restricted Use product 

EPA Reg. No. 100-

RUAL 

Mixed formulation capsule suspension and 

suspension concentrate (0.65%) 

0.061

Ground Corn (field corn, see

corn, yellow popcorn a

1Also contains atrazine: 1.0 lb/gal., mesotrione: 0.24 lb/gal., and S-metolachlor: 2.14 lb/gal. 
-Page 68 of 88- 

Appendix B. Bicyclopyrone and its Environmental Transformation Products Table B1. Bicyclopyrone and its Environmental Transformation Products: Structures and Maximum Con

Code Name Chemical Name Chemical Structure Study Type MRID(s) Maxim

%AR (d

PARENT

NOA449280 Bicyclopyrone 

IUPAC: 4-hydroxy-3-[2-(2-methoxy-ethoxymethyl)-6-trifluoromethyl-pyridine-3-carbonyl]-bicyclo[3.2.1]oct-3-en-2-one CAS: 4-hydroxy-3-[[2-[(2-methoxyethoxy)methyl]-6-(trifluoromethyl)-3-pyridinyl]carbonyl]bicyclo[3.2.1]oct-3-en-2-one CAS No. 352010-68-5 Formula: C19H20F3NO5

MW: 399.36 g/mol

SMILES Code:COCCOCc1c(ccc(n1)C(F)(F)F)C(=O)C2=C(C3CCC(C3)C2=O)O 

O CF3

N

OH O

O

OMe

Aerobic Soil 

Metabolism 

47842026478420334784203447842035

Not App

Anaerobic 

Soil 

Metabolism 

47842027

Aerobic 

Aquatic 

Metabolism 

4784207347842074

Anaerobic 

Aquatic 

Metabolism 

4784207347842074

Soil 

Photodegrada

tion 

4784202847842029

Hydrolysis 47841919 

Aqueous 

Photolysis 47841921

Terrestrial 

Field 

Dissipation 

478420384784203947842040
-Page 69 of 88- 

Code Name Chemical Name Chemical Structure Study Type MRID(s) Maxim

%AR (d

MAJOR DEGRADATES 

CSCC163768 SYN504810 

IUPAC: 6-(Trifluoromethyl)pyridine2,3-dicarboxylic acid CAS: 6-trifluoromethylpyridine-2,3-dicarboxylic acidCAS No. 90376-94-6 MW: 235.1 g/mol Formula: C8 H4F3NO4

SMILES: c1cc(nc(c1C(=O)O)C(=O)O)C(F)(F)F 

N

F

F

F

O

HO

O OH

Aqueous 

Photolysis 47841921

26.6@ pH 

2.9@ pH 

3.0 nat.w

Soil 

Photolysis 

47842029 11.7-17

15)

47842028 9.6 (3

835.4100 

Aerobic Soil 

Metabolism

47842033

(7 soils)D ND-0.9 

47842034

(5 soils)D 0.7-1.2 

47842035 

(4 soils) 

0.1(3, 1

1.5(9

835.4300 

Aerobic 

Aquatic 

Metabolism

47842073 1.7-2.8 

*NonGuideline* 

Aer. Aquatic 

Metab. + 

Photodeg. 

47842075 43.4 (29

(16

835.4400 

Anaerobic 

Aquatic 

Metabolism

47842073 8.3-9.1 

835.6100 

Terrestrial 

Field 

Dissipation 

478420384784203947842040

6.2 (

ND ND 
-Page 70 of 88- 

Code Name Chemical Name Chemical Structure Study Type MRID(s) Maxim

%AR (d

CSAA456156 CGA375529 

IUPAC: 6-Trifluoro-methylpyridine-3-carboxylic acid 

CAS: 6-Trifluoromethylpyridine-2,3-dicarboxylic acid

Formula: C7H4F3NO2

MW: 191.108 g/mol SMILES: c1cc(ncc1C(=O)O)C(F)(F)F 

*NonGuideline* 

Aer. Aquatic 

Metab. + 

Photodeg. 

47842075 19.7-20.

CSAA589691 (NOA412101) 

IUPAC: (1S,3R)-Cyclopentane-1,3-dicarboxylic acid CAS: (1S,3R)-Cyclopentane1,3-dicarboxylic acid CAS No. 876-05-1 Formula: C7 H10 O4 MW: 158.1 g/mol SMILES: C1CC(CC1C(=O)O)C(=O)O 

HO

O

O HO Aqueous Photolysis 47841921

26.3@pH 

18.7@ pH 

14.5 nat

(30

Soil 

Photolysis 47842028 1.4 (

CSCD642512 (SYN545859) 

IUPAC: 2-[[3-(2,4-Dioxobicyclo[3.2.1]octane-3-

Soil 

Photolysis 47842029 2.2-4.1 
-Page 71 of 88- 

Code Name Chemical Name Chemical Structure Study Type MRID(s) Maxim

%AR (d

carbonyl)-6-(trifluoromethyl)-2-pyridyl]methoxy]acetic acid

CAS: [3-(2-Hydroxy-4-oxobicyclo[3.2.1]oct-2-ene-3-carbonyl)-6-trifluoromethylpyridin-2-ylmethoxy]-acetic acid Formula: C18H16F3NO6

MW: 399.3 g/mol SMILES:c1cc(nc(c1C(=O)C2C(=O)C3CCC(C3)C2=O)COCC(=O)O)C(F)(F)F 

 47842028 6.2 (3

835.4100 

Aerobic Soil 

Metabolism

47842033

(7 soils)D

0.7 (35

(120

O

N

O

O

F

F

F

OH O

OH 47842034

(5 soils)D

1.2 (50

(120

47842035

(4 soils) 

1.2 (28)

(92

835.4200 

Anaerobic 

Soil 

Metabolism

47842027 2.9 (8

835.6100 

Terrestrial 

Field 

Dissipation 

478420384784203947842040

ND 

2.5 (

0.7 (1

CSCD656832* IUPAC: 3-Hydroxy-6- Soil 47842029 7.0-8.0 (
-Page 72 of 88- 

Code Name Chemical Name Chemical Structure Study Type MRID(s) Maxim

%AR (d

(SYN545680) *This compound will be included as a residue of concern in the ecological risk 

assessment. 

(trifluoromethyl)pyridine-2-carboxylic acid CAS: 3-Hydroxy-6-trifluoromethyl-pyridine-2-carboxylic acid Formula: C7H4F3NO3

MW: 207.1 g/mol SMILES: c1cc(nc(c1O)C(=O)O)C(F)(F)F

Photolysis 

47842028 4.8 (3

835.4100 

Aerobic Soil 

Metabolism

47842033

(7 soils)D 2.8-9.8 

47842034

(5 soils)D

0.1(7

14.4(1

47842035

(4 soils) 0.2(64)-1

835.6100 

Terrestrial 

Field 

Dissipation 

478420384784203947842040

11.8 (

ND ND 

SYN503780 (CSAA794148) 

IUPAC: 2-(2-Methoxyethoxymethyl)-6-(trifluoromethyl)-nicotinic acid CAS: 3-pyridinecarboxylic 

Aqueous 

Photolysis 47841921

6.3@ pH 2.9@ pH 

4.9 nat.w

Soil 

Photolysis 47842029 35.8-62

15)
-Page 73 of 88- 

Code Name Chemical Name Chemical Structure Study Type MRID(s) Maxim

%AR (d

acid, 2-[(2-methoxyethoxy)methyl]-6-(trifluoromethyl)- Formula: C11H12F3NO4

MW: 279.2 g/mol SMILES: COCCOCc1c(ccc(n1)C(F)(F)F)C(=O)O

47842028 25.3 (

835.4100 

Aerobic Soil 

Metabolism

47842033

(7 soils)D

0.5 (120

(50

47842034

(5 soils)D 0.6 (7)- 4

47842035

(4 soils) 1.4(92)-

835.4200 

Anaerobic 

Soil 

Metabolism

47842027 3.4 (6

835.4300 

Aerobic 

Aquatic 

Metabolism

47842073 2.3 (105

(60

*NonGuideline* 

Aer. Aquatic 

Metab. + 

Photodeg. 

47842075 3.4 (3)-4

835.4400 

Anaerobic 

Aquatic 

Metabolism

47842073 3.8 (182

(91
-Page 74 of 88- 

Code Name Chemical Name Chemical Structure Study Type MRID(s) Maxim

%AR (d

835.6100 

Terrestrial 

Field 

Dissipation 

478420384784203947842040

7.9 (

20.4 (

14.0 

CO2 Carbon dioxide 

Formula: CO2

MW: 44.1 g/mol

SMILES: O=C=O 

O

O

Aqueous 

Photolysis 47841921

4.7 @ pH 4.7 @ pH 

0.6 nat.w

Soil 

Photolysis 

47842029 1.8-2.5 (

47842028 20.1 (

835.4100 

Aerobic Soil 

Metabolism

47842026

(1 soil) 75.8 (3

47842033 

(7 soils)D 4.8-44.1 

47842034

(5 soils)D 10.7-65.8 

47842035

(4 soils) 

11.4 (120

(120

835.4200 

Anaerobic 

Soil 

Metabolism

47842027 8.7 (8

835.4300 

Aerobic 

aquatic 

metabolism

47842073 1.0-1.4 

47842074 2.6 (60

(105

*NonGuideline* 

Aer. Aquatic 

Metab. + 

Photodeg. 

47842075 0.5-4.3 

835.4400 

Anaerobic 

Aquatic 

Metabolism

47842073 0.2-0.3 

47842074 3.1 (182

(365
-Page 75 of 88- 

Code Name Chemical Name Chemical Structure Study Type MRID(s) Maxim

%AR (d

MINOR DEGRADATES

CSAA806573 (NOA451778) 

IUPAC: 2-Hydroxymethyl-6-

trifluoromethyl-nicotinic acid 

CAS: 2-Hydroxymethyl-6-trifluoromethyl-nicotinic acid Formula: C8 H6 F3 N O3 MW: 221.1 g/mol SMILES: c1cc(nc(c1C(=O)O)CO)C(F)(F)F N

O

HO

CF3

OH

Aqueous 

Photolysis 47841921

5.5@ pH 

ND @ 

2.3 nat.w

835.4200 

Anaerobic 

Soil 

Metabolism

47842027 1.2 (1

835.4400 

Anaerobic 

Aquatic 

Metabolism

47842073 0.5-2.0 

835.6100 

Terrestrial 

Field 

Dissipation 

478420384784203947842040

2.1 (

ND 

3.5 (

CSAA915194 (NOA454598) 

IUPAC: 4-Hydroxy-3-[2-(2-

hydroxy-ethoxymethyl)-6-trifluoromethyl-pyridine-3-carbonyl]-bicyclo[3.2.1]oct-3-en2-one

CAS: 4-Hydroxy-3-[2-(2-hydroxy-ethoxymethyl)-6-trifluoromethyl-pyridine-3-carbonyl]-bicyclo[3.2.1]oct-3-en-2-one Formula: C18H18F3NO5

MW: 385.3g/mol SMILES: 

c1cc(nc(c1C(=O)C2=C(C3CCC(C3)C2=O)O)COCCO)C(F)(F)F

835.4300 

Aerobic 

Aquatic 

Metabolism

47842073 1.6-2.0 

*NonGuideline* 

Aer. Aquatic 

Metab. + 

Photodeg. 

47842075 7.1-7.6 

835.4400 

Anaerobic 

Aquatic 

Metabolism

47842073 1.2 (365

(182

OH

O

N

O

O OH

CF3
-Page 76 of 88- 

Appendix C. SWCC Results 

SWCC Output File 

Variable Volume Water Model, SWCC Compatible Version 

 

 ******************************************* 

Performed on: 9/ 9/2014 at 13:44 

 

Peak 1-in-10 = 4.04 ppb 

Chronic 1-in-10 = 3.09 ppb 

Simulation Avg = 2.30 ppb 

4-day avg 1-in-10 = 4.03 ppb 

21-day avg 1-in-10 = 4.01 ppb 

60-day avg 1-in-10 = 3.92 ppb 

90-day avg 1-in-10 = 3.83 ppb 

 

Benthic Pore Water Peak 1-in-10 = 3.50 ppb 

Benthic Pore Water 21-day avg 1-in-10 = 3.50 ppb 

Benthic Conversion Factor = 0.960 -Pore water (ug/L) to 

(total mass, ug)/(dry sed mass,kg) 

Benthic Mass Fraction in Pore Water = 0.386 

 

YEAR Peak 4-day 21-day 60-day 90-day Yearly Avg 

Benthic Pk Benthic 21-day 

 1 8.38E-01 8.35E-01 8.29E-01 8.07E-01 7.88E-01 4.34E-01 

6.74E-01 6.74E-01 

 2 9.73E-01 9.70E-01 9.65E-01 9.40E-01 9.20E-01 7.75E-01 

8.55E-01 8.54E-01 

 3 9.54E-01 9.52E-01 9.44E-01 9.23E-01 9.02E-01 8.06E-01 

8.64E-01 8.63E-01 

 4 1.76E+00 1.75E+00 1.73E+00 1.69E+00 1.65E+00 1.22E+00 

1.47E+00 1.47E+00 

 5 2.63E+00 2.63E+00 2.60E+00 2.54E+00 2.48E+00 1.94E+00 

2.24E+00 2.24E+00 

 6 3.69E+00 3.68E+00 3.65E+00 3.57E+00 3.48E+00 2.76E+00 

3.16E+00 3.16E+00 

 7 2.97E+00 2.97E+00 2.95E+00 2.95E+00 2.98E+00 2.73E+00 

3.00E+00 3.01E+00 

 8 2.55E+00 2.55E+00 2.54E+00 2.48E+00 2.48E+00 2.30E+00 

2.51E+00 2.53E+00 

 9 3.51E+00 3.50E+00 3.46E+00 3.42E+00 3.35E+00 2.68E+00 

3.06E+00 3.06E+00 

 10 3.03E+00 3.02E+00 2.99E+00 2.93E+00 2.87E+00 2.69E+00 

2.88E+00 2.89E+00 

 11 3.59E+00 3.58E+00 3.55E+00 3.47E+00 3.39E+00 2.84E+00 

3.16E+00 3.16E+00 

 12 2.81E+00 2.81E+00 2.82E+00 2.84E+00 2.87E+00 2.53E+00 

2.90E+00 2.92E+00 

 13 2.64E+00 2.64E+00 2.61E+00 2.55E+00 2.49E+00 2.24E+00 

2.39E+00 2.39E+00 

 14 4.08E+00 4.07E+00 4.05E+00 3.96E+00 3.87E+00 3.00E+00 

3.51E+00 3.51E+00 
-Page 77 of 88- 

 15 3.23E+00 3.23E+00 3.24E+00 3.26E+00 3.29E+00 2.90E+00 

3.32E+00 3.33E+00 

 16 4.68E+00 4.67E+00 4.63E+00 4.51E+00 4.41E+00 3.42E+00 

3.98E+00 3.98E+00 

 17 4.25E+00 4.24E+00 4.20E+00 4.09E+00 3.99E+00 3.65E+00 

3.89E+00 3.89E+00 

 18 3.33E+00 3.33E+00 3.33E+00 3.36E+00 3.39E+00 3.03E+00 

3.44E+00 3.46E+00 

 19 2.67E+00 2.67E+00 2.66E+00 2.63E+00 2.66E+00 2.45E+00 

2.71E+00 2.73E+00 

 20 2.29E+00 2.28E+00 2.26E+00 2.21E+00 2.20E+00 2.05E+00 

2.24E+00 2.25E+00 

 21 2.41E+00 2.40E+00 2.38E+00 2.33E+00 2.28E+00 2.00E+00 

2.17E+00 2.17E+00 

 22 3.68E+00 3.67E+00 3.64E+00 3.56E+00 3.49E+00 2.73E+00 

3.17E+00 3.17E+00 

 23 3.66E+00 3.66E+00 3.63E+00 3.58E+00 3.51E+00 3.10E+00 

3.36E+00 3.36E+00 

 24 3.17E+00 3.16E+00 3.14E+00 3.08E+00 3.02E+00 2.83E+00 

3.02E+00 3.04E+00 

 25 2.83E+00 2.83E+00 2.80E+00 2.74E+00 2.69E+00 2.50E+00 

2.66E+00 2.65E+00 

 26 2.30E+00 2.30E+00 2.30E+00 2.31E+00 2.33E+00 2.08E+00 

2.36E+00 2.37E+00 

 27 2.16E+00 2.15E+00 2.13E+00 2.08E+00 2.04E+00 1.84E+00 

1.97E+00 1.97E+00 

 28 2.52E+00 2.52E+00 2.50E+00 2.44E+00 2.38E+00 1.99E+00 

2.20E+00 2.20E+00 

 29 1.97E+00 1.97E+00 1.98E+00 1.99E+00 2.01E+00 1.81E+00 

2.04E+00 2.05E+00 

 30 1.81E+00 1.81E+00 1.80E+00 1.77E+00 1.73E+00 1.58E+00 

1.69E+00 1.69E+00 

**************************************************************************

************************** 

 Effective compartment halflives averaged over simulation duration: 

 

 zero washout 0 

 water col metab halflife (days) = 997.620816648772 

 zero hydrolysis 0 

 photolysis halflife (days) = 6714.02721266894 

 volatile halflife (days) = 1852047775.80744 

 total water col halflife (days) = 868.562743557013 

 

 zero burial 0 

 zero benthic metab 0 

 zero benthic hydrolysis 0 

 zero benthic total degradation 0 

 *********************************************************************** 

 Fractional Contribution of Transport Processes to Waterbody & Total Mass 

(kg): 

 

 Due to Runoff = 0.9629 0.4315 

 Due to Erosion = 0.0037 0.1637E-02 

 Due to Drift = 0.0335 0.1500E-01 
-Page 78 of 88- 

 *********************************************************************** 

 Flow in/out Characteristics of Waterbody: 

 Average Daily Runoff Into Waterbody (m3/s) = 6.652821823241803E-004 

 Baseflow Into Waterbody (m3/s) = 0.000000000000000E+000 

 Average Daily Flow Out of Waterbody (m3/s) = 6.652821823241945E-004 

 *********************************************************************** 

 Inputs: 

 14.75 = oc partitioning coefficient 

 667.2 = water column half Life 

 20.00 = reference temp for water column degradation 

 0.000 = benthic Half Life 

 20.00 = Reference temp for benthic degradation 

 2.000 = Q ten value 

 50.10 = photolysis half life 

 40.00 = reference latitude for photolysis study 

 0.000 = hydrolysis half life 

 399.4 = molecular wt 

 0.3800E-07 = vapor pressure 

 0.1190E+06 = solubility 

 0.1000E+06 = field area 

 0.1000E+05 = water body area 

 2.000 = initial depth 

 2.000 = maximum depth 

 2 1=vvwm, 2=usepa pond, 3 = usepa reservoir, 4 = const vol no 

flow, 5 = const vol w/flow 

 F T = burial, else no burial 

 0.1000E-07 = mass transfer coefficient 

 0.5000 = PRBEN 

 0.5000E-01 = benthic compartment depth 

 0.5000 = benthic porosity 

 1.350 = benthic bulk density 

 0.4000E-01 = OC frcation in benthic sediment 

 5.000 = DOC in benthic compartment 

 0.6000E-02 = benthic biomass 

 1.190 = DFAC 

 30.00 = SS 

 0.5000E-02 = chlorophyll 

 0.4000E-01 = OC frcation in water column SS 

 5.000 = DOC in water column 

 0.4000 = biomass in water column 

 FRACTION AREA CROPPED = 1.00000000000000 

 

Summary of Water Modeling of Bicyclopyrone and the USEPA 

Standard Pond 

Estimated Environmental Concentrations for bicyclopyrone are presented in Table 1 for the 

USEPA standard pond with the NECornStd field scenario. A graphical presentation of the yearto-year peaks is presented in Figure 1. These values were generated with the Surface Water 

Concentration Calculator (SWCC Version 1.106). Critical input values for the model are 

summarized in Tables 2 and 3. 

This model estimates that about 3% of bicyclopyrone applied to the field eventually reaches the 
-Page 79 of 88- 

water body. The main mechanism of transport from the field to the water body is by runoff 

(96.3% of the total transport), followed by spray drift (3.35%) and erosion (0.37%). 

In the water body, pesticide dissipates with an effective water column half-life of 868.6 days. 

(This value does not include dissipation by transport to the benthic region; it includes only 

processes that result in removal of pesticide from the complete system.) The main source of 

dissipation in the water column is metabolism (effective average half-life = 997.6 days) followed 

by photolysis (6714 days) and volatilization (1.852048E+09 days). 

In the benthic region, pesticide is stable. Most of the pesticide in the benthic region (61%) is 

sorbed to sediment rather than in the pore water. 

Table 1. Estimated Environmental Concentrations (ppb) for bicyclopyrone. 

Peak (1-in-10 yr) 4.04 

4-day Avg (1-in-10 yr) 4.03 

21-day Avg (1-in-10 yr) 4.01 

60-day Avg (1-in-10 yr) 3.92 

365-day Avg (1-in-10 yr) 3.09 

Entire Simulation Mean 2.30 

Table 2. Summary of Model Inputs for bicyclopyrone. 

Scenario NECornStd 

Cropped Area Fraction 1 

KdF (ml/g) 0.59 

Water Half-Life (days) @ 20 °C 667.2 

Benthic Half-Life (days) @ 20 °C 0 

Photolysis Half-Life (days) @ 40 

°Lat 

50.1 

Hydrolysis Half-Life (days) 0 

Soil Half-Life (days) @ 20 °C 213.2 

Foliar Half-Life (days) 0 

Molecular Wt 399.4 

Vapor Pressure (torr) 3.8e-8 

Solubility (mg/l) 119e3 

Table 3. Application Schedule for bicyclopyrone. 

Date (Days 

Since 

Type Amount (kg/ha) Eff. Drift 
-Page 80 of 88- 

Emergence) 

-7 Ground 0.05 0.99 0.01 

Figure 1. Yearly Peak Concentrations 

 
-Page 81 of 88- 

Appendix D. Groundwater Modeling Results 

SCIGROW Output

 

SCIGROW

                          VERSION 2.3

            ENVIRONMENTAL FATE AND EFFECTS DIVISION

                 OFFICE OF PESTICIDE PROGRAMS

             U.S. ENVIRONMENTAL PROTECTION AGENCY

                        SCREENING MODEL

                FOR AQUATIC PESTICIDE EXPOSURE

  

SciGrow version 2.3

chemical:bicyclo 2

time is  8/21/2014  11:46:13

 ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐ 

  Application      Number of       Total Use    Koc      Soil Aerobic

  rate (lb/acre)  applications   (lb/acre/yr)  (ml/g)   metabolism (days)

 ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐ 

      0.045           1.0           0.045      7.00E+00      125.5

 ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐ 

groundwater screening cond (ppb) =   1.32E+00  

************************************************************************

  

PRZM-GW Output 

Groundwater Analysis for Bicyclopyrone and the Wisconsin Corn - 

WI Central Sands Scenario

Estimated groundwater concentrations and breakthrough times for bicyclopyrone are presented 

in Table 1 for the Wisconsin Corn - WI Central Sands groundwater scenario. A graphical 

presentation of the daily concentrations in the aquifer is presented in Figure 1. These values were 

generated with the PRZM-GW (Version 1.07). Critical input values for the model are 

summarized in Tables 2 and 3. To achieve breakthrough to groundwater, an extended weather 

file (100 years) was used, as breakthrough did not occur using the standard 30-yr modeling run. 

Table 1. Groundwater Results for Bicyclopyrone and the Wisconsin Corn - WI Central 

Sands Scenario. 

Peak Concentration (ppb) 7.95 

Post-Breakthrough Mean 

Concentration (ppb) 

 7.33 

Entire Simulation Mean 

Concentration (ppb) 

 5.05 

Average Breakthrough 

Time (days) 

12079.23 

Throughputs 2.993735 
-Page 82 of 88- 

Table 2. Chemical Properties for Groundwater Modeling of Bicyclopyrone. 

Kd (ml/g) 0.59 

Surface Soil Half Life (days) 213.2 

Hydrolysis Half Life (days) 0 

Diffusion Coefficint Air (cm2/day) 0.0 

Henry's Constant 0.0 

Enthalpy (kcal/mol) 0.0 

Table 3. Pesticide application scheme used for Bicyclopyrone. This application scheme was 

applied every year of the simulation. 

Application Date 

(Month/Day) 

Application Method Application Rate 

(kg/ha) 

04/30 Ground application with mass 

distribution increasing 

proportionally with depth to 4 cm 

0.05 

Figure 1. Aquifer Breakthrough Curve for Bicyclopyrone and the Wisconsin Corn - WI 

Central Sands Scenario 
-Page 83 of 88- 

Appendix E. Example STIR (v. 1.0) input and output data 

 
-Page 84 of 88- 

Appendix F. Ecotoxicity data gaps and uncertainties Table 1. Aquatic ecotoxicity data gaps and uncertainties. 

Guideline Data Requirement Test Substance MRID EPA Study Classification 

Are 

Additional 

Data 

Needed? 

850.1350 Estuarine/marine invertebrates life-cycle NOA449280 TGAI (94.5%) No1 850.1400 Estuarine/marine fish early-life stage NOA449280 TGAI (94.5%) -- -- No1 

N/A = Data are not available 1 ACR values have been calculated in absence of data Table 2. Terrestrial ecotoxicity data gaps and uncertainties. 

Guideline Data Requirement Test Substance MRID EPA Study Classification 

Are 

Additional 

Data 

Needed? 
-Page 85 of 88- 

Guideline Data Requirement Test Substance MRID EPA Study Classification 

Are 

Additional 

Data 

Needed? 

850.2100 

Acute oral toxicity to 

birds 

Canary 

(Serinus canaria) 

NOA449280 

TGAI 

(94.5%) 

47842078 Supplemental Yes LD50 = 

OECD 237 

and NonGuideline 

Honey bee larval acute 

and chronic oral 

toxicity 

NOA449280 

TGAI 

(94.5%) 

-- -- Yes 

NonGuideline Honey bee adult chronic oral toxicity NOA449280 TGAI (94.5%) -- -- Yes 
-Page 86 of 88- 

Appendix G. Example T-REX (v. 1.5.2) input and output data 

TREX MODEL INPUTS You must enable macros for this spreadsheet to work correctly

These values will be used in the calculation of exposure estimates for foliar, granular, liquid and/or 

seed applications of pesticides.

Application No. Rate

Chemical Name: Application Rate (lb ai/acre) 1

Seed Treatment? (Check if yes) FALSE Seeding Rate (lbs/acre) 2

 Use: 3

Product name and form: 4

% A.I. (leading zero must be entered for 

formulations <1% a.i.): 5

Application Rate (lb ai/acre) 0.045 6

Half-life (days): 35 7

Application Interval (days): 8

Number of Applications: 1 9

Are you assessing applications with 

variable rates or intervals? no 10

11

12

What body weight range is assessed 

(grams)? Birds Mammals 13

Small 20 15 14

Medium 100 35 15

Large

1000 1000 16

17

18

19

94.50%

Assessed Species Inputs (optional, use defaults for RQs for national level 

assessments)

You MUST specify application day in Columns F and G - you may enter up to 30 applications

Chemical Identity and Application Information

Bicyclopyrone

Corn

Bicyclopyrone

Avian

Endpoint Toxicity value

Indicate test species 

below

Optional Test 

Organism Body 

weight (g) Optional Test Species Name Toxicity Value Reference (MRID)

LD50 (mg/kg-bw) 1206.00 1

LC50 (mg/kg-diet) 5550.00 2

NOAEL (mg/kg-bw) 1

NOAEC (mg/kg-diet) 35.00 2

1.15

Mammalian 1

Acute Study Chronic Study

350 350

Endpoint Toxicity value Reference (MRID)

LD50 (mg/kg-bw) 5000.00

LC50 (mg/kg-diet)

Reported Chronic Endpoint 2.15 1

Is dietary concentration 

(mg/kg-diet) reported from the 

available chronic mammal 

study? (yes or no)

yes

yes

Enter dietary concentration 

(mg/kg-diet) 25.00

Estimated Chronic Diet 

Concentration Equivalent to 

Reported Chronic Daily Dose

25

mg/kg-diet based on 

standard FDA lab rat 

conversion

Enter the Mineau et al. Scaling Factor

Size (g) of mammal used in toxicity study

mg/kg-bw

Bobwhite quail

Mallard duck

Bobwhite quail

Mallard duck
-Page 87 of 88- 

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

20 868.84 11.62 0.01 5.33 0.01 6.54 0.01 0.73 0.00 4.55 0.01 0.16 0.00

100 1106.07 6.63 0.01 3.04 0.00 3.73 0.00 0.41 0.00 2.60 0.00 0.09 0.00

1000 1562.37 2.97 0.00 1.36 0.00 1.67 0.00 0.19 0.00 1.16 0.00 0.04 0.00

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

5550 10.21 0.00 4.68 0.00 5.74 0.00 0.64 0.00 4.00 0.00

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

35 10.21 0.29 4.68 0.13 5.74 0.16 0.64 0.02 4.00 0.11

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

15 10989.15 9.73 0.00 4.46 0.00 5.47 0.00 0.61 0.00 3.811167106 0.0003 0.1351 1E-05

35 8891.40 6.73 0.00 3.08 0.00 3.78 0.00 0.42 0.00 2.634026337 0.0003 0.0934 1E-05

1000 3845.80 1.56 0.00 0.71 0.00 0.88 0.00 0.10 0.00 0.610708241 0.0002 0.0217 6E-06

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

0 10.21 #DIV/0! 4.68 #DIV/0! 5.74 #DIV/0! 0.64 #DIV/0! 4.00 #DIV/0!

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

25 10.21 0.41 4.68 0.19 5.74 0.23 0.64 0.03 4.00 0.16

Table X. Upper Bound Kenaga, Acute Mammalian Dietary Based Risk Quotients

EECs and RQs

Arthropods

Table X. Upper Bound Kenaga, Chronic Mammalian Dietary Based Risk Quotients

EECs and RQs

Arthropods

Size class not used for dietary risk quotients 

NOAEC 

(ppm)

Size class not used for dietary risk quotients

Arthropods

Table X. Upper Bound Kenaga, Chronic Avian Dietary Based Risk Quotients

EECs and RQs

Broadleaf Plants

EECs and RQs

EECs and RQs

Summary of Risk Quotient Calculations Based on Upper Bound Kenaga EECs

Arthropods

Short Grass

Size class not used for dietary risk quotients 

NOAEC 

(ppm)

Tall Grass

LC50 

(ppm)

Short Grass

Size 

Class

(grams)

Adjusted

LD50 Short Grass

Fruits/Pods/Seed

s Tall Grass

Arthropods

Adjusted

LD50

Size class not used for dietary risk quotients

Table X. Upper Bound Kenaga, Acute Mammalian Dose-Based Risk Quotients 

LC50

Tall Grass Broadleaf Plants Fruits/Pods/Seeds Granivore

Arthropods

Short Grass Tall Grass Broadleaf Plants Fruits/Pods/Seed

Broadleaf Plants Fruits/Pods/Seed

s

Short Grass Tall Grass Broadleaf Plants Fruits/Pods/Seed

s

Broadleaf Plants Fruits/Pods/Seeds Granivore

Table X. Upper Bound Kenaga, Acute Avian Dose-Based Risk Quotients

EECs and RQs

Short Grass Tall Grass Size 

Class

(grams)

Table X. Upper Bound Kenaga, Subacute Avian Dietary Based Risk Quotients
-Page 88 of 88- 

Appendix H. Example TerrPlant (v. 1.2.2) input and output data    

TerrPlant v. 1.2.2

Green values signify user inputs (Tables 1, 2 and 4). 

Input and output guidance is in popups indicated by red arrows.

Parameter

Chemical Name

PC code

Use

Application Method

Application Form

Solubility in Water (ppm)

Input Parameter Symbol Value (user inputs) Units

Application Rate A 0.045 lbs ai/A

Incorporation I 1 none

Runoff Fraction R 0.05 none

Drift Fraction D 0.01 none

Equation EEC

(A/I)*R 0.00225

(A/I)*R*10 0.0225

A*D 0.00045

((A/I)*R)+(A*D) 0.0027

((A/I)*R*10)+(A*D) 0.02295

Plant type EC25 NOAEC EC25 NOAEC 

Monocot 0.074 0.067 0.02 0.017

Dicot 0.005 0.002 0.001 0.0002

Plant Type Listed Status Dry Semi-Aquatic Spray Drift

Monocot non-listed <0.1 0.31 <0.1

Monocot listed <0.1 0.34 <0.1

Dicot non-listed 0.54 4.59 0.45

Dicot listed 1.35 11.48 2.25

Table 3. EECs for Bicyclopryone. Units in lbs ai/A.

Runoff to dry areas

Runoff to semi-aquatic areas

Spray drift

Total for dry areas

Table 1. Chemical Identity.

Bicyclopryone

Corn

Table 2. Input parameters used to derive EECs.

Ground Spray

liquid

119000

18986

User Inputs

*If RQ > 1.0, the LOC is exceeded, resulting in potential for risk to that plant group.

Seedling Emergence Vegetative Vigor

Table 5. RQ values for plants in dry and semi-aquatic areas exposed to Bicyclopryone through runoff 

and/or spray drift.*

Table 4. Plant survival and growth data used for RQ derivation. Units are in lbs ai/A. All values are user 

inputs

Description

Total for semi-aquatic areas