UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

 WASHINGTON, D.C. 20460

 OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

DP Barcode: 398130 

PC Code: 555550 

February 3, 2012 

MEMORANDUM

SUBJECT: Cyflufenamid: Addendum to the Ecological Risk Assessment on cucurbit 

vegetables (crop group 9), low growing berry (crop subgroup 12-07G) except 

cranberries, pome fruit (crop subgroup 11), outdoor landscape and outdoor 

nursery ornamentals, and small fruit vine climbing except fuzzy kiwifruit (crop 

subgroup 13-07F) for the treatment of powdery mildew (DP 360841, September 

3, 2010). 

TO: Mark Suarez, Product Manager 13 

Samantha Hulkower, Risk Reviewer 

Insecticide Branch 

Registration Division (7505P) 

 

THROUGH: Dana S. Spatz, Chief 

Rosanna Louie-Juzwiak, Risk Assessment Process Leader 

Environmental Risk Branch III 

Environmental Fate and Effects Division (7507P) 

FROM: Amy Blankinship, Chemist 

Environmental Risk Branch III 

Environmental Fate and Effects Division (7507P) 

 

The Environmental Fate and Effects Division (EFED) previously completed an ecological risk 

assessment (DPs 360841 and 366391, September 3, 2010) for the new fungicide, cyflufenamid, 

for use on cucurbit vegetables, low growing berry except cranberries, pome fruit, outdoor 

landscape and outdoor nursery ornamentals, and small fruit vine climbing except fuzzy kiwifruit 

for the treatment of powdery mildew. 

The risk assessment identified several ecotoxicity and environmental fate data needs, which are 

summarized in Table 1.
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Table 1. Ecological Effects and Environmental Fate Data Needs 

Aquatic invertebrate life-cycle (freshwater) OPPTS 850.1300 

Aquatic invertebrate life-cycle (saltwater) OPPTS 850.1350 

Fish early-life stage (saltwater) OPPTS 850.1400 

Aquatic plant growth (cyanobacteria and green algae) OPPTS 850.5400 

Seedling emergence – Tier II for tomato, cabbage, oat, and soybean OPPTS 850.4100 

Chronic invertebrate whole sediment study using the TGAI (two freshwater species: a midge 

and an amphipod; one estuarine species: an amphipod) 

Identification of VOC-2 from MRID 47620715 

Additional characterization is provided below for each of the ecotoxicity studies listed in Table 

1. Additionally, EPA has since received additional information for consideration, specifically, 

an OECD 219 sediment toxicity study using the midge, Chironomus riparius, tested using spiked 

water as well as an acute toxicity study with the common carp (Cyprinus carpio). Although 

there are several uncertainties associated with each of the previously identified ecological effects 

and environmental fate studies, based on the weight of evidence, EPA believes that risk to 

nontarget organisms is not expected for the proposed uses. To confirm the conclusions reported 

in the previous ecological assessment, as well as the additional characterization presented in this 

memo, data are being requested as outlined below as confirmatory data. 

Aquatic invertebrate life-cycle (freshwater) OPPTS 850.1300 

In the previous risk assessment (DP360841;366391), chronic toxicity data for freshwater 

invertebrates were not available as the submitted study was classified as unacceptable due to 

excessive control mortality (MRID 47620704). The registrant submitted an additional chronic 

life-cycle toxicity test with Daphnia magna (MRID 48274002); however again, mortality in one 

of the control groups exceeded the validity criteria. As such, as stand-alone studies, neither of 

these studies are adequate for use in a risk assessment. However, when considered together, they 

present similar information on length, which is a sensitive endpoint. Given the current 

application rates and the calculated EECs, the NOAEC value of 0.0998 mg a.i./L (99.8 μg a.i./L) 

is approximately 217 times greater than the EEC. However, if in the future, an increase in 

application rate is proposed, then the use of this NOAEC value will need to be re-evaluated. 

It does not appear that conducting an additional test would provide any added value for the risk 

assessment and therefore, the NOAEC for the daphnia chronic study of 0.0998 mg a.i./L can be 

used to assess the proposed uses. The MRID 48274002 study is classified as Supplemental. 

Additionally, study #1 (MRID 47620704) will be upgraded to Supplemental. Further details of 

the review of these two studies are presented in the DER memo for 48274002 and the DER 

addendum for 47620704. 

 
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Aquatic invertebrate life-cycle (saltwater), OPPTS 850.1350 

Chronic toxicity data for estuarine-marine (saltwater) invertebrates are not available. Based on 

the risk assessment, acute risk to estuarine-marine invertebrates is not expected. The method of 

applying an acute-to-chronic ratio (ACR), using data from freshwater invertebrates to estimate 

chronic estuarine-marine toxicity cannot be used here as there was less than 50% 

immobility/mortality observed in the daphnia acute test, which was conducted at or above the 

limit of solubility (EC50 > 1.73 mg a.i. (total)/L; 15% immobility at this concentration). As 

stated above, the NOAEC for the chronic freshwater invertebrates is 0.0998 mg a.i./L which is 

approximately 217 times greater than the chronic EEC. The acute EC/LC50 values for estuarinemarine invertebrates are 0.16 mg a.i./L (160 μg a.i./L) (oyster) and 0.64 mg a.i. (total)/L (640 μg 

a.i. (total)/L) (mysid shrimp) which suggests that estuarine-marine invertebrates appear to be 

more sensitive than freshwater invertebrates on an acute basis. There is uncertainty in the mysid 

acute value as the study was conducted at the apparent limit of solubility and did not measure the 

dissolved fraction. For a chronic LOC exceedance for estuarine-marine invertebrates, the 

chronic toxicity NOAEC would have to be 0.46 μg a.i./L or lower which is approximately 348 

times lower than the lowest acute estuarine-marine toxicity value. Given the magnitude between 

the EECs and the necessary chronic toxicity value for estuarine-marine invertebrates, as well as 

the observed differences for the chronic daphnia value and EECs, chronic risk to estuarinemarine invertebrates is not expected for the proposed uses. 

Fish early-life stage (ELS) (saltwater), OPPTS 850.1400 

Chronic (ELS) toxicity data for estuarine-marine (saltwater) fish are not available. The ACR 

approach, as described above, may also be used to estimate chronic toxicity to estuarine-marine 

fish. Typically, the ACR is calculated using the acute and chronic freshwater fish studies from 

the same species but there are no available acute toxicity study conducted on the fathead 

minnow, nor was a chronic rainbow trout study available. Additionally, the actual toxicity is 

uncertain for the effects observed in the chronic freshwater fish study because endpoints were 

based on total cyflufenamid (both dissolved and undissolved); the chronic NOAEC for the 

fathead minnow is 0.2 mg a.i. (total)/L (200 μg a.i.(total)/L) based on survival. However, to 

exceed the chronic LOC, the chronic NOAEC value for freshwater and/or estuarine-marine fish 

would have to be 0.22 μg a.i./L which is 913 times lower than the current chronic NOAEC for 

fathead minnow (based on total cyflufenamid concentrations). Acute toxicity values were 

available for three freshwater fish (rainbow trout, bluegill and common carp) and the estuarinemarine sheepshead minnow (Table 2). Based on the available data, the LC50 for warmwater fish 

appears to be greater than the limit of solubility, and therefore testing the warmwater fathead 

minnow may also result in a non-definitive LC50 value, which would preclude the ability to 

conduct an ACR evaluation. In addition, as there was no mortality at the limit of solubility for 

sheepshead minnow, a comparison of toxicity to freshwater fish cannot be made. However, 

given the large difference between the observed toxicity in the chronic fathead minnow study 

and the EEC as well as the observed toxicity for warmwater fish, the uncertainty in not having 

estuarine-marine chronic toxicity data is likely a minor issue in the overall risk conclusions for 

the proposed uses. 
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Table 2. Acute toxicity values for fish for cyflufenamid 

Species LC50 (mg 

a.i./L) MRID Comments 

Rainbow trout 1.04 47620626 Acceptable 

Bluegill sunfish >1.2 47620625 

Supplemental due to 

inversion of test 

concentrations; no mortality 

at highest concentration 

Common carp >0.968 48715502 

Preliminary review; no 

mortality at highest 

concentration 

Sheepshead minnow >0.20 47670702 Acceptable; no mortality at 

highest concentration 

 ` 

Aquatic plant growth (cyanobacteria and green algae), OPPTS 850.5400 

Direct effects to non-vascular aquatic plants may result in indirect effects to other taxa as an 

impact to their food source and/or habitat. Currently, there are no Federally listed nonvascular 

plant species. 

As stated in the risk assessment, based on available data, the RQs (based on toxicity to the 

freshwater diatom, Navicula) for listed aquatic plants do not exceed the LOC for any of the 

proposed uses. For evaluation to non-listed plants, given that the available data resulted in no 

effect at the limit concentration (the EC50 is a greater than value), RQ values were not calculated. 

However, the EECs for the proposed uses (≤0.85 ug ai/L) are at least 316 times less than the 

limit concentration for Navicula (269 ug ai/L). Acceptable toxicity data were not available for 

two of the four required species (i.e., cyanobacteria and green algae studies) and there was 

uncertainty about toxicity in the Skeletonema study because the measured concentrations are 

based on total (dissolved and undissolved) cyflufenamid and so toxicity may be underestimated. 

In addition there is no available information on the mode of action for this pesticide which could 

be used to make inferences about toxicity to other algal species from the Navicula and 

Skeletonema studies. The submitted cyanobacteria and green algae studies were unacceptable 

because the use of a solvent may have promoted growth and therefore potentially mask effects of 

cyflufenamid. For the green algae, the promotion of growth in the solvent control was 11% 

compared to the negative control. Based on the reported green algae NOAEC = 1.4 mg a.i./L 

(1,400 μg a.i./L) and the EEC (0.85 μg a.i./L), the observed promotion of growth will likely not 

influence the overall conclusions for non-vascular plants. For the cyanobacteria study, the 

reported NOAEC was 0.245 mg a.i./L (245 μg a.i./L) which is approximately 288 times greater 

than the EEC. However, in this study, an ca. 70% promotion of growth was observed in the 

solvent control and the dose-response curve for the treatment groups is an inverted U-shaped 

curve (typically a relatively straight-line is optimal), therefore it is difficult to make any adequate 

inferences about this study in relation to the EECs. 

Evaluation of non-vascular aquatic plants is used to evaluate potential aquatic community effects 

due to a potential change in food source or habitat parameters. Based on the evaluation above, it 

appears that for three of the four required test species, potential direct adverse risk to non-
5 

vascular aquatic plants is not likely. However, given the difficulties in interpreting the 

cyanobacteria study, this study is requested to confirm that there is no direct risk to non-vascular 

plants. 

850.4225 - (referred to as 850.4100 in assessment which is Tier I study) Seedling 

Emergence, Tier II for Tomato, Cabbage, Oat, Soybean 

As stated in the assessment, risk to non-listed terrestrial plants is not expected. In addition, risk 

to listed plants is also not expected based on the vegetative vigor study (MRID 47620710) and 

six of the 10 requested plant species for the seedling emergence study (MRID 47620709). 

However, this assessment of risk to listed terrestrial plants is based on an incomplete dataset. 

For the seedling emergence study, a NOAEC or EC05 was not established for four plant species 

(i.e., tomato, cabbage, oat and soybean), and therefore a Tier II seedling emergence study was 

requested for these species to establish a NOAEC or EC05. In the seedling emergence study, two 

concentrations were tested at application rates 1.6 to 2 times higher than the maximum proposed 

application rate, however, a dose-response relationship was not observed for all species, which 

makes it harder to make inferences about potential effects in relation to exposure concentrations. 

The NOAEC or EC05 is used to evaluate risk to listed terrestrial plants and in turn any potential 

indirect effects to other taxa based on an obligate/dependant relationship to a listed plant. 

Overall, based on the available data, risk to listed plants is not expected, however, this 

conclusion is based on an incomplete dataset and data for the four remaining plant species are 

requested to confirm that listed plants are not expected to be at risk. 

Chronic invertebrate whole sediment studies: (two freshwater species: a midge and an 

amphipod; one estuarine species: an amphipod) 

Based on the fate and physical properties of cyflufenamid, it has the potential to bind to sediment 

and be persistent in the aquatic environment. A comparison of available aquatic invertebrate 

acute toxicity data (i.e., EC50 >1.73 mg a.i./L, Daphnia magna and LC50 = 0.65 mg a.i./L, mysid 

shrimp, 0.16 mg a.i./L, Eastern oyster) to the sediment pore water peak EEC (0.132 μg/L) 

indicates that the pore water EEC is at least 1,200 times lower than the acute water-column 

toxicity data. A comparison of the chronic Daphnia NOAEC value (0.0998 mg a.i./L) to the 21-

day pore water EEC (0.129 μg/L) indicates that the EEC is ca. 770 times lower than the chronic 

value. 

The registrant submitted a 28 day sediment invertebrate study using the midge, Chironomus 

riparius, which followed OECD Guideline 219, using spiked water (MRID 48715502). There 

were effects on emergence and developmental rate and time at the highest concentration tested 

(0.67 mg a.i./L, overlying water; 0.036 mg a.i./L, pore water; 7.64 mg/kg, sediment). The 

NOAEC was 0.37 mg a.i./L overlying water and 0.036 mg a.i./L pore water and 8.8 mg/kg 

sediment. This NOAEC value is expected to be an overestimation for the pore water and 

sediment concentrations as analytical measurements over the 28 day test period in the high and 

low treatment groups showed an increase (partitioning) to the sediment and pore water; however, 

pore water and sediment were only analyzed on Day 28 for the other test concentrations, which 

includes the concentration used to establish the NOAEC. In addition, per the test protocol, 20 

immature midges were to be placed into each test vessel; however, emergence of more than 20 
6 

organisms was observed for many of the vessels with numbers ranging from 21 to 27. Therefore, 

there is uncertainty in determining an effect on percent emergence if there is uncertainty in the 

actual number of organisms exposed. A comparison of the pore water NOAEC to the pore EEC 

(36 vs. 0.129 μg a.i./L) shows that the EEC is ca. 280 times lower than the NOAEC; this 

suggests risk may be low to Chironomus sp. 

The original request for sediment toxicity data in the risk assessment asked for data on two 

freshwater organisms (Chironomus tentans and Hyallela azteca) and an estuarine-marine 

organism (Leptochirus plumulosus). If the results of the midge study above are representative of 

the Chironomus sp. sensitivity, then further testing with this Genus is not necessary. Also based 

on the results of the acute and chronic Daphnia and the sediment midge test, chronic testing may 

not be the appropriate first step. Therefore, a tiered approach is now recommended. It is 

recommended that first acute toxicity to the other two requested species be conducted to evaluate 

their sensitivity compared to the water column invertebrate and midge toxicity data, as well as a 

predicted EECs. Studies could be conducted following the 850.1020 acute amphipod guideline. 

If it is deemed that further testing is warranted, then the next step may be to conduct subchronic 

testing using guidelines OPPTS 850.1735 and 850.1740 and then again evaluate to determine if 

further testing is warranted. However, if it is believed that chronic testing would be more 

suitable after analysis of the acute data, then going straight to chronic testing may be requested.