### 1 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

PC Codes : 108800

108801

DP Barcode : D426907

Date : May 8, 2015

MEMORANDUM

Subject: Response to Public Comments on the EFED Registration Review Problem

Formulation for Metolachlor and S-Metolachlor

To: Steven Snyderman, Risk Review Manager
Avivah Jacob, Team Leader Kelley Sherman, Acting Branch Chief Risk Management and Implementation Branch 3 Pesticide Re-Evaluation Division (7508P)

From: Robin Sternberg, Wildlife Biologist Christopher M. Koper, Chemist

Environmental Risk Branch 1 Environmental Fate and Effects Division (7507P) Office of Pesticide Programs

Through: Sujatha Sankula, Ph.D., Branch Chief

Environmental Risk Branch 1 Environmental Fate and Effects Division (7507P) Office of Pesticide Programs

In response to the preliminary “Registration Review Problem Formulation for Metolachlor and SMetolachlor” (DP 420467), Syngenta provided comm ents during the public comment period. The purpose of this memorandum is to address comments that are applicable to EFED’s problem formulation.

Syngenta:

EPA statement Table 6-1. Page 20 S-metolachlor (CGA-24705) Chronic estuarine/marine invertebrate; Mysid Shrimp; NOAEC (mg/L) 0.00013. Syngenta Comment: The chronic estuarine/marine invertebrate endpoint appears to be a typographical error. We believe the correct value should be 0.13 mg a.i./L (MRID 44995902) as

described in Table 6- 2 (page 24) of the Prelimi nary Problem Formulation.

EFED response: EFED concurs with the comment. The chronic estuarine/marine invertebrate NOAEC endpoint for S-metolachlor (MRID 44995902) should be 0.130 mg a.i./L in Table 6-1.

### 2 Syngenta:

EPA statement Table 6-2. Page 22 Mammalian acute oral; S-Metolachlor; rat ( Rattus norvegicus );combined sexes LD 50 = 3267 mg/kg bw, Male LD 50

= 2577 m g /k g bw

, Female LD 50 = 2672 m g /k g bw ; MRID Syngenta Comment: There appears to be a typographical error with the endpoints. We believe the correct values should be 2672 mg/kg bw, 3267 mg/kg bw, and 2577 mg/kg bw for combined sexes, males, and females, respectively.

EFED response: EFED concurs with the comment. The acute oral mammalian LD 50 endpoints for S-metolachlor (MRID 43928915) should be 3267, 2577, and 2672 mg/kg-bw for males, females, and the sexes combined, respectively, Table 6-2.

Syngenta:

EPA statement Table 6-2, Page 23 and Appendix D, Page 83 Freshwater invertebrate acute: 48 hours, static; Metolachlor (% a.i. not reported); Water flea ( Ceriodaphnia dubia ); EC 50 (95% C.I.) =

1.1 ( 0.9-1.4 ) m g /L ; E067777 ; Quantitative ( Foste r et al.

, 1998 ) Syngenta Comment: Based on recommendations in the “Evaluation Guidelines for Ecological Toxicity Data in the Open Literature” (US EPA 2011), the data from E067777 are not of sufficient quality to justify their use quantitatively in ecological risk assessment. This conclusion is based on study specific deficiencies related to the reporting of important methodological details and experimental results as well as a substantial lack of agreement between the endpoints presented in E067777 with other scientifically valid (GLP-sourced) lines of evidence.

Notably, E067777 does not specify the source (m anufacturer) or purity (% active ingredient) of test substance. While chemical analysis me thods are described in E067777, no analytical data are provided and exposure levels are never detailed. The study must indicate the exact nature and source of the pesticide and failure to do so br ings the validity of the study results into question (US EPA 2011).

To be used quantitatively, the endpoints reported in open literature must provide sufficient

information to substantiate and/or allo w independent evaluation of whether a dose-dependent response is evident and endpoints are accurate. E067777 does not provide this information and concern related to these deficiencies are further heightened given that no raw data wereprovided and endpoints reported by E067777 do not align with other scientifically valid (GLPsourced) lines of evidence. Specifically, endpoints presented in E067777 are >20 times lower (suggesting markedly greater biological activity ) than similar aquatic invertebrate endpoints from both registrant submitted GLP studies (MRID 00015546 = 25.1 mg a.i./L) and data from an U.S. Fish and Wildlife database (Mayer 1986 = 23.5 mg a.i./L [TGAI] and 26.0 mg a.i./L [TEP]). Similarly, while there are deficiencies described in subsequent comments for E083887 that preclude its use quantitatively for ecological risk assessment, the researchers reported 24-h

LC 50 values of >50 mg a.i./L for studies with Daphnia magna

.

While the difference in endpoints could conceivabl y be due to differences in species sensitivity (E067777 used Ceriodaphnia dubia while other endpoints are for D. magna ), other data described in E067777 also do not align when simila r comparisons using the same species are made for other active ingredients. For instance, the C. dubia malathion endpoint reported in

### 3 E067777 was four-times lower than the endpoint reported by Ankley et al. (1991). Likewise, the

C. dubia endpoint for atrazine obtained in E067777 was 7-times lowe r than the endpoint reported by Oris et al. (1991).

The lack of agreement between the endpoints repor ted by E067777 and other studies could be due to impurities in the test material, errors in mixing treatment concentrations, incorrect use of appropriate test chamber material (test cham bers are not described by E067777), or poor test organism health. Overall, the major exper imental deficiencies with E067777 and lack of agreement with other lines of evidence strongly i ndicate that it is not appropriate to rely on endpoints from E067777 for quantitativ e risk assessment (US EPA 2011).

Taking the aforementioned information into consideration, Syngenta strongly believes that data from MRID 00015546 (acute freshwater invertebrate endpoint = 25.1 mg a.i./L) should be applied quantitatively for ecological risk assessments.

Ankley GT, Dierkes JR, Jensen DA, and Peterson GS. 1991. Piperonyl butoxide as a tool in aquatic toxicology research with or ganophosphate insecticides. Ecotoxicology and Environmental Safety 21: 266-274.

Mayer F, Ellersieck M. 1986. Manual of Acut e Toxicity: Interpretation and Data Base 410 Chemicals and 66 Species of Freshwater Animals. US Fish and Wildlife Service; Resource Publication (160): 579 p.

Oris JT, Winner RW, and Moore MV. 1991. A fou r-day survival and reproduction toxicity test for Ceriodaphnia dubia. Environmental Toxicology and Chemistry 10: 217-224.

US EPA. 2011. Evaluation Guidelines for Ecolog ical Toxicity Data in the Open Literature. Office of Chemical Safety and Pollution Prevention. May 9, 2011.

EFED response: After additional review, EFED agrees that E067777 should not be used for quantitative assessment because the study authors did not report purity (% active ingredient) of the test substance lending uncertainty as to what the test organisms were exposed. The study will be used qualitatively in the risk charac terization. The endpoint from MRID 00015546 (EC 50 = 25.1 mg/L; Table 1) will now be considered the most sensitive quantitative endpoint from acute freshwater invertebrate toxicity studies with metolachlor/S-metolachlor. Data from MRID 40098001 (Mayer and Ellersieck, 1986) may be used quantitatively if, after review, the data are deemed appropriate for quantitative assessment.

Table 1. Most Sensitive Endpoint from Acut e Freshwater Invertebrate Toxicity Studies

with Metolachlor/S-Metolachlor

Study Type Test

Substance (% a.i.) Species Toxicity Endpoints and Acute Toxicity Classification (If Applicable) Source & Study

Classification

Freshwater

invertebrate

acute: 48

hours Metolachlor

technical (NS) Water flea ( Daphnia

magna ) EC 50 (95% C.I.) = 25.1 (21.6-29.2) mg

a.i./L NOAEC = 5.6 mg a.i./L LOAEC = 10 mg a.i./L (NOAEC based no mortality at 5.6 mg/L)

Slightly toxic MRID 00015546 Acceptable

### 4 Syngenta:

EPA statement Table 6-2, Page 23 and Appendix D, Page 83-84 Freshwater invertebrate life cycle: 21 days, static renewal; Metolachlor (% a.i. not reported); Water flea ( Daphnia magna ); NOAEC = 0.001 mg/L (nom); LOAEC = 0.01 mg/L (nom) (based on number of

young pe r female); E083887; Quantitative (Liu et al., 2006). Syngenta Comment: Based on recommendations in the “Evaluation Guidelines for Ecological Toxicity Data in the Open Literature” (US EPA 2011), the data from E083887 are not of sufficient quality to permit their use quantitatively in ecological risk assessment. This conclusion is based on study specific deficiencies related to the reporting of important methodological details and experimental results as well as a substantial lack of agreement between the endpoints presented in E083887 with other, scientifically valid (GLP-sourced) lines of evidence.

While E083887 does specify the purity of the test substance (95.3% and 96% for rac- and Smetolachlor, respectively), it does not de scribe the source (manufacturer). The study must indicate the exact nature and source of the pesticide and failure to do so brings the validity of the study results into question according to US EPA (2011). In addition, while it was determined in a pretest that both enantiomers were stable in stock solutions after one week, stock concentrations were not analytically confirmed at the beginning of the exposure or after weekly renewals during the exposure. Concentrations of test material used during the exposure were not verified for any treatment and the study did not specify the frequency of test solution renewal. Moreover, E083887 does not provide any water quality data.

Available data from two studies (MRI D 46322101, 43802601) comple ted by two different independent GLP-certified contract research laboratories starkly contrast with the results of E083887. Each of these studies reported NOAEC values for Daphnia exposed to either metolachlor or S-metolachlor yielding endpoints of 3.2 mg a.i./L and 5.17 mg a.i./L, respectively. The data from E083887 do not align with this available information as the endpoints for racemic and S-metolachlor were 3200x and 51x lower, respectively, in E083887 compared to those from GLP studies. The large magnitude of differ ence between thes e endpoints may be explained by error in mixing test solutions during the E083887 study as the open literature study did not confirm concentration in the exposure solutions.

It is also important to emphasize that a comparison of available data for all other animal tests (Table 6-1 of the preliminary problem formulation) does not show a substantial difference in toxicity between racemic and S-metolachlo r approaching anything close to the 100-fold

difference described in E083887. This lack of bi ological difference in enantiomer specifictoxicity is also demonstrated for other compounds of similar structure (such as dimethenamid and dimethenamid-P). Furthermore, no chemicals in the chloroacetamide pesticide class (of which metolachlor is a member, as well as acetochlor, alachlor, and dimethenamid) demonstrate reproductive effects on D. magna at any concentrations close to those reported by E083887.

Overall, the results from E083887 do not align with any of these other lines of evidence. Therefore, the endpoints from E083887 are considered an outlier. As such, it is not appropriate to use data from E083887 qualitatively for ecological risk assessment. Taking the

aforementioned information into consideration, Syngenta prop oses that data from MRID 46322101 (chronic freshwater invertebrate endpoint = 3.2 mg a.i./L) and MRID 43802601 (chronic freshwater invertebrate endpoint = 5.17 mg a.i./L) represent the best available data and therefore should be applied quant itatively for ecological ri sk assessments and the endpoint

referenced from E083887 should be charac terized as scientifically invalid.

### 5 US EPA. 2011. Evaluation Guidelines for Ecolog ical Toxicity Data in the Open Literature. Office of Chemical Safety and Pollution Prevention. May 9, 2011.

EFED response: After additional review, EFED agrees that E083887 should not be used for quantitative assessment because the study authors only quantified test substance concentrations during a “pretest determination” rather than the actual test lending uncertainty asto whether the large discrepancy in results between the open literature study and registrantsubmitted studies (where concentrations were measured) was due to experimental error in the preparation of test solutions in the former study (E083887). The study will be used qualitatively in the risk characterization. The endpoint from MRID 43802601 (NOAEC = 3.2 mg/L; Table 2) will now be considered the most sensitive quant itative endpoint from chronic freshwater invertebrate toxicity studies with metolachlor/S-metolachlor.

Table 2. Most Sensitive Endpoint from Chr onic Freshwater Invertebrate Toxicity Studies

with Metolachlor/S-Metolachlor

Study Type Test

Substance (% a.i.) Species Toxicity Endpoints and Acute Toxicity Classification (If Applicable) Source & Study

Classification

Freshwater

invertebrate life cycle: 21 days, flow through (chronic) Metolachlor

technical (97) Water flea ( Daphnia

magna ) NOAEC = 3.2 mg a.i./L (m) LOAEC = 6.9 mg a.i./L (m) (NOAEC based reductions in growth and reproduction)

Note: Due to variability in the measured concentrations, the endpoints are based on the lowest

measured concentration at each

treatment level. MRID

43802601 Supplemental (due to

uncertain

exposure concentrations

lack of raw growth data)

Syngenta:

EPA statement Section 8.1.2. Page

30. Following the recommendation of the Residues of ConcernKnowledgebase Subcommittee (ROCKS), parent metolachlor, CGA51202 (metolachlor-OA), CGA-40172, and CGA-50720 will be assessed together in the drinking water assessment using a total toxic residues (TTR) approach and will follow the latest guidance and methodology (USEPA, 2014c, D424250). Syngenta Comment: Previous EFED drinking water assessments of S-metolachlor have relied on a combination of monitoring data (where available) and modeling (where the available data were not sufficient to assess a proposed new use). EPA has provided guidance for the use of monitoring data: “When reliable aquatic monitoring data are available, EPA uses these data to help characterize the levels of pesticides that are being detected in the environment.” ( http://www.epa.gov/oppefed1/ecorisk_ders/toera_analysis_exp.htm ; website updated February 13, 2015).

The USGS National Water-Quality Assessment (NAWQA) Program has provided sufficient data for the assessment of parent S-metolachlor in surface and ground waters for many years, along

with other state and federal water monitori ng programs. Syngenta encourages EPA to continue to rely on these data in future drinking water assessments, supplemented by modeling of degradates of concern as necessary.

### 6 EFED response: The Agency will continue to use a combination of modeling and monitoring data as appropriate. Although the U.S. Geological Survey’s National Water Quality Assessment (NAWQA) program has conducted some monitoring for metolachlor/S-metolachlor and itsdegradates, the NAWQA monitoring data are not targeted specifically to metolachlor/Smetolachlor use areas or during times of known metolachlor/S-metolachlor use; thus, the dataset does not likely reflect peak concentrations that may occur in surface waters when runoff events occur shortly after metolachlor/S-metolachlor is applied.

Syngenta:

EPA statement Table 11-2. Page

37-38. Non-guideline. Whole sediment: Chronic invertebrates, freshwater

and marine.

Modeling via the Surface Water Concentration Calculator (SWCC, v. 1.106) indicates peak and 21-day pore water EECs of up to 41.9 and

41.8 μ g/L, respectively. Although the peak pore water concentration is approximately 0.04 of the LC 50 of 1100 μ g/L for D. magna (E067777), the 21-day pore water EEC is 41 * NOAEC of 1 μ g/L for D. magna (E083887). According to toxicity testing and ecological risk assessment guidance for benthic invertebrates (USEPA, 2014b), if the 21-day pore water EEC ≥ 1.0 * chronic water column NOAEC, the

need fo r chronic sediment toxicit y testin g is indicated. Syngenta Comment: Previous comments highlight study specific deficiencies related to the reporting of important methodological details and ex perimental results as well as a substantial lack of agreement between the endpoints pres ented in E067777 and E083887 with other lines of

evidence. These deficiencies and la ck of agreement with other lines of evidence indicate that data from E067777 and E083887 are not appropriate to use quantitatively for the purposes of ecological risk assessment. Taking this information into consideration, the best available data for characterizing potential effects on freshw ater aquatic organisms are from MRID 00015546 (acute freshwater invertebrate endpoint = 25.1 mg a.i./L), MRID 46322101 (chronic freshwater invertebrate endpoint = 3.2 mg a.i./L), and MRID 43802601 (chronic freshwater invertebrate endpoint = 5.17 mg a.i./L). For estuarine/marine species, the most sensitive acute endpoint is from MRID 42378901 (Eastern oyster LC 50 = 1.6 mg a.i./L) and the most sensitive chronic endpoint is from MRID 44995902 (Mysid chronic NOAEC = 0.13 mg/L).

For conservative screening level evaluation, the endpoints from the estuarine/marine studies should be used to evaluate the need for chronic sediment toxicity tests. Comparing the acute endpoint from MRID 42378901 to the peak pore water concentration described by the EPA (41.9

μ g/L) yields a risk quotient of 0.03 (41.9 μ g/L /1600 μ g/L = 0.026). Comparing the chronic endpoint from MRID 44995902 to the peak pore water concentration described by the EPA (41.8

μ g/L) yields a risk quotient of 0.32 (41.8 μ g/L /130 μ g/L = 0.32). Both of these screening level risk quotients are below their corre sponding levels of conc ern (acute = 0.1; chronic = 1; US EPA 2014). Sediment toxicity testing data is available for sediment-spiked studies with Chironomus riparius in which the LC 50 and NOAEC values are >160 mg/kg dry sediment (Grade 1998). Assuming Koc values of 135 and 219 described in the Preliminary Problem Formulation, these endpoints can be conver ted to >29600 and >18200 μ g/L (pore water).

### 7 Based on the toxicity testing and ecological risk assessment guidance for benthic invertebrates (USEPA 2014), the results of this screening level evaluation using the best available data do not indicate the need for chronic sediment toxicity testing. Syngenta is submitting the referenced C. riparius study report concurrently to EPA.

Grade R. 1998. CGA 77102. Acute toxicity test of CGA 77102 tech. on sediment-dwelling Chironomus riparius (syn. Chironomus thummi ) under static conditions. Project Number: 971562. Unpublished study conducted by Novartis Crop Protection AG, Basel Switzerland.

USEPA. 2014. Toxicity Testing and Ecological Risk Assessment Guidance for Benthic Invertebrates. Environmental Fate and Effects Division. Office of Pesticide Programs. April 10,

2014.

EFED response: Since the study that triggered the need for chronic sediment toxicity testing ( i.e. , E083887) is only sufficient for qualitative use in the risk characterization, EFED concurs with the comment and agrees that chronic sediment toxicity testing is not needed at this time. The submitted study by Grade (1998) will be reviewed and classified for use in the upcoming Registration Review risk assessment.

Syngenta:

EPA statement Section 9. Page 31 Consistent with the Agency’s responsibility under the Endangered Species Act (ESA), the Agency will evaluate risks to federally listed threatened and/or endangered (listed) species from registered uses of pesticides in Registration Review. The process for evaluating potential risks to listed species is further described at http://www.epa.gov/oppfead1/endager/litstatus/riskasses.htm. Syngenta Comment: Simple deterministic screening level assessments, which are highly conservative by design, can facilitate rapid initial screening/exclusion criteria for a pesticide active ingredients’ potential to adversely affect listed (t hreatened or endangered species) and non-listed species. If a pesticide exposure resu lts in a risk quotient (RQ) below a predefined level of concern (LOC), which are additionally conservative with respect to endangered (listed) species assessments (e.g. 5x to 10x lower than already conservative non-listed LOCs), then the potential risks are considered de minimis and unlik ely to jeopardize the existence of a listed species. Thus by design, su ch compounded layers of conserva tism are intended to minimize potential type II errors (failure to reject a false null hypothesis of de minimus risk) but correspondingly compound unrealisti c conditions and assumptions.

If, however, an RQ is generated that exceeds the highly conservative LOC, additional higher-tier scientific information must be incorporated in order to refine the risk assessment and more accurately and realistically refl ect potential exposures and effect s, and reducing potential type I errors (falsely rejecting the null hypothesis of de minimus risk). This information includes community-level effects data, environmental fa te and exposure data, monitoring data, geospatial location and proximity data, species biology data, and a variety of refined modelling and assessment analysis, and other pertinent spec ies-specific and pesticide-specific data.

Given that ‘risk’ requires esti mation of likelihood, higher tier risk assessments need to consider and employ probabilistic techniques in order to mo re accurately and rea listically characterize risk. Moreover, where possible and appropriate , risk assessments should consider assemblage level effects (populations, communities, and eco systems) rather than singular deterministically

### 8 oriented single species approaches. A summary of the types of higher-tier data and assessment refinements available to more accurately and realistically evaluate potential risks to endangered species is provided in MRID# 49200601 and Brain et al. (2015). Syngenta is submitting a courtesy copy of this publication concurrently to EPA.

Reference: Brain R, Teed S, Bang J, Thorbek P, Perine J, Peranginangin N, Kim M, Valenti T, Chen W, Breton R, Rodney S, and Moore D. 20 15. Risk Assessment Considerations With Regard to the Potential Impacts of Pesticides on Endangered Species. Integrated Environmental Assessment and Management 11: 102-117.

EFED response: The Agency will evaluate risks to federally listed threatened and endangered (listed) species from registered uses of pesticides in accordance with the Joint Interim Approaches developed to implement the recommendations of the April 2013 National Academy of Sciences (NAS) report, Assessing Risks to Endangered and Threatened Species from

Pesticides . The NAS report outlines recommendations on specific scientific and technical issues related to the development of pesticide risk assessments that EPA and the Services must conduct in connection with their obligati ons under the Endangered Species Act (ESA) and FIFRA. EPA will address concerns specific to metolachlor/S-metolachlor in connection with the development of its final Registration Review decision for metolachlor/S-metolachlor

.

In November 2013, EPA, the U.S. Fish and Wildlife Service, National Marine Fisheries (the Services), and USDA released a white paper

, Interim Approaches for National-Level Pesticide Endangered Species Act Assessments Based on the Recommendations of the National Academy of Sciences April 2013 Report

, containing a summary of their joint Interim Approaches for assessing risks to listed species from pesticides. These Interim Approaches were developed jointly by the agencies in response to the NAS recommendations, and reflect a common approach to risk assessment shared by the agencies as a way of addressing scientific

differences between the EPA and the Services.

Given that the agencies are continuing to develop and work toward implementation of the Interim Approaches to assess the potential risks of pesticides to listed species and their designated critical habitat, this ecological problem formulation supporting the Preliminary Work

Plan for metolachlor/S-metolachlor did not describe the specific ESA analysis, including effects determinations for specific listed species or designated critical habitat, to be conducted during Registration Review. While the agencies continue to develop a common method for ESA analysis, the planned risk assessment for the Registration Review of metolachlor/S-metolachlor will describe the level of ESA analysis completed for this particular Registration Review case.

This assessment will allow EPA to focus its future evaluations on the types of species where the potential for effects exists, once the scientific methods being developed by the agencies have been fully vetted. Once the agencies have fu lly developed and implemented the scientific methods necessary to complete risk assessments for listed species and their designated critical habitats, these methods will be applied to subsequent analyses of metolachlor/S-metolachlor as part of completing Registration Review.

Syngenta:

EPA statement Table 6-2. Page 24-25 Referenced endpoints for aquatic non-vascular and vascular plant studies are presented as cell density and/or frond density, respectively.

### 9 Syngenta Comment: Effective concentrations (EC X ) calculated based on growth rate are considered more robust than those based on standing crop (cell density and biomass) for a given time-point since growth rate is independent of exposure time (EPA 2012). For aquatic plants, study duration, conditions of temperature, light, and nutrients, and reported endpoints can vary considerably among studies. Other resource limiting factors, such as nutrient depletion and self-shading, can complicate the in terpretation of reported plant EC X ’s. These factors may affect
study results, which could resu lt in biased estimates in cert ain cases for some species (EPA 2012). Using absolute biomass can potentially result in particularly misleading EC X ’s when
growth rates are modest, and a departure from exponential gr owth will be most pronounced in the treatments with the highest growth rates (EPA 2012). With respect to toxicity testing, differences in design of the study can result in complicated growth dynamics and relationships that are difficult to interpret and apply (EPA 2012).

As indicated by Bergtold and Dohmen (2011), the Organization for Economic Cooperation and Development (OECD) indicates a clear preference for growth rate as the appropriate endpoint in the lemna and algal toxicity test guideline (OE CD 2006a, b). Specifically, the OECD guideline for testing growth inhibition in freshwater alga and cyanobac teria (OECD 2006a) states:

“EC X values based upon average specific growth rate (E
r C

X

) will generally be higher than results based upon yield (E y C X

) if the test conditions of this Guideline are adhered to, due to the mathematical basis of the respective approaches. This should not be interpreted as a difference in sensitivity between the two response variables, simply that the values are different mathematically. The concept of average specific growth rate is based on the general exponential growth pattern of algae in non-limited cultur es, where toxicity is esti mated on the basis of the effects on the growth rate, without be ing dependent on the absolute level of the specific growth rate of the control, slope of the concentration-response curve or on test duration. In contrast, results based upon the yield response variable are dependent upon all these other variables. [Yield] is dependent on the specific growth rate of the algal species used in each test and on the maximum specific growth rate that can vary between species and even different algal strains.

This response variable should not be used for comparing the sensitivity to toxicants among algal species or even different strains.”

Based on the aforementioned information, relative growth rate is the most appropriate aquatic plant endpoint for ecological risk assessment.

Bergtold, M. and G.P. Dohmen. 2011. Biomass or growth rate endpoint for algae and aquatic plants: Relevance for the aquatic risk assessment of herbicides. Integr. Environ. Assess. Manag. 7: 237-247.

OECD (Organization for Economic Cooperation and Development). 2006a. OECD Guideline 201: Freshwater alga and cyanobacteria, growth inhibition test. Adopted 23 March 2006. Paris.

OECD (Organization for Economic Cooperation and Development). 2006b. OECD Guideline 221: Lemna sp. growth inhibition test. Adopted 23 March 2006. Paris.

US EPA, 2012. Proposed Methodology for Specifying Atrazine Levels of Concern for Protection of Plant Communities in Freshwater Ecosystems. Report To: Environmental Fate and Effects Division, Office of Pesticide Progr ams, U.S. Environmental Protection Agency, Washington, DC. EPA/600/R-12/019. Mid-Continent Ecology Division, National Health and Ecological Effects

### 10 Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Duluth, MN. March 5, 2012.

EFED response: The argument provided by Syngenta regarding use of growth rate as the most appropriate endpoint for ecological risk assessment is noted. EFED still anticipates using the most sensitive aquatic plant endpoints to calculate Risk Quotients (RQs), regardless of whether the endpoints are based on growth rate or standing crop.