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 comments 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 Preliminary 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 LD50 = 3267 mg/kg bw, Male LD50 

= 2577 mg/kg bw, Female LD50 = 2672 mg/kg 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 LD50 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); EC50 (95% C.I.) = 

1.1 (0.9-1.4) mg/L; E067777; Quantitative (Foster 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 (manufacturer) or purity (% active ingredient) of

test substance. While chemical analysis methods 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 brings 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 allow 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 were

provided 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

LC50 values of >50 mg a.i./L for studies with Daphnia magna. 

While the difference in endpoints could conceivably 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 similar comparisons using the same species are

made for other active ingredients. For instance, the C. dubia malathion endpoint reported in
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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 lower than the endpoint

reported by Oris et al. (1991). 

The lack of agreement between the endpoints reported 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 chambers are not described by E067777), or poor test

organism health. Overall, the major experimental deficiencies with E067777 and lack of

agreement with other lines of evidence strongly indicate that it is not appropriate to rely on

endpoints from E067777 for quantitative 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 organophosphate insecticides. Ecotoxicology and

Environmental Safety 21: 266-274. 

Mayer F, Ellersieck M. 1986. Manual of Acute 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 four-day survival and reproduction toxicity test for 

Ceriodaphnia dubia. Environmental Toxicology and Chemistry 10: 217-224. 

US EPA. 2011. Evaluation Guidelines for Ecological 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 characterization. The endpoint from MRID 00015546 (EC50 = 

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 Acute 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) 

EC50 (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 
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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 per 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 describe 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 (MRID 46322101, 43802601) completed 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 difference between these 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-metolachlor approaching anything close to the 100-fold

difference described in E083887. This lack of biological 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 proposes 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 quantitatively for ecological risk assessments and the endpoint 

referenced from E083887 should be characterized as scientifically invalid. 
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US EPA. 2011. Evaluation Guidelines for Ecological 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 as 

to 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 quantitative endpoint from chronic freshwater 

invertebrate toxicity studies with metolachlor/S-metolachlor. 

Table 2. Most Sensitive Endpoint from Chronic 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 Concern

Knowledgebase 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 monitoring 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. 
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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 its 

degradates, 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 μg/L, respectively. Although the peak pore water concentration is

approximately 0.04 of the LC50 of 1100 μg/L for D. magna (E067777),

the 21-day pore water EEC is 41 * NOAEC of 1 μg/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 for chronic sediment toxicity testing is indicated. 

Syngenta Comment: Previous comments highlight 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 and E083887 with other lines of 

evidence. These deficiencies and lack 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 freshwater 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 LC50= 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 

μg/L) yields a risk quotient of 0.03 (41.9 μg/L /1600 μg/L = 0.026). Comparing the chronic

endpoint from MRID 44995902 to the peak pore water concentration described by the EPA (41.8 

μg/L) yields a risk quotient of 0.32 (41.8 μg/L /130 μg/L = 0.32). Both of these screening level 

risk quotients are below their corresponding levels of concern (acute = 0.1; chronic = 1; US EPA 

2014). Sediment toxicity testing data is available for sediment-spiked studies with Chironomus 

riparius in which the LC50 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 converted to >29600 and >18200 μg/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 (threatened or endangered species) and

non-listed species. If a pesticide exposure results 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 unlikely to jeopardize the existence of a listed

species. Thus by design, such compounded layers of conservatism are intended to minimize

potential type II errors (failure to reject a false null hypothesis of de minimus risk) but

correspondingly compound unrealistic 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 reflect potential exposures and effects, and reducing potential type I

errors (falsely rejecting the null hypothesis of de minimus risk). This information includes

community-level effects data, environmental fate 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 species-specific and pesticide-specific data. 

Given that ‘risk’ requires estimation of likelihood, higher tier risk assessments need to consider

and employ probabilistic techniques in order to more accurately and realistically characterize

risk. Moreover, where possible and appropriate, risk assessments should consider assemblage

level effects (populations, communities, and ecosystems) rather than singular deterministically
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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. 2015. 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 obligations 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 fully developed and implemented the scientific 

methods necessary to complete risk assessments for listed species and their designated critical 

habitats, these methods will be applied to subsequent analyses of 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 (ECX) 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 interpretation of reported plant ECX’s. These factors may affect 

study results, which could result in biased estimates in certain cases for some species (EPA 

2012). Using absolute biomass can potentially result in particularly misleading ECX’s when

growth rates are modest, and a departure from exponential growth 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 (OECD 2006a, b). Specifically, the OECD guideline for 

testing growth inhibition in freshwater alga and cyanobacteria (OECD 2006a) states: 

“ECX values based upon average specific growth rate (ErCX) will generally be higher than results 

based upon yield (EyCX) 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 cultures, where toxicity is estimated on the basis of the

effects on the growth rate, without being 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 Programs, 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.