1 OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460

May 3 , 2016

PC Code: 128993

MEMORANDUM DP Barcodes: 432534

SUBJECT: Cyproconazole : Response to Comments on the EFED Problem Formulation for Registration Review

FROM: Elyssa Arnold, Risk Assessment Process Leader

Environmental Risk Branch 2 Environmental Fate and Effects Division (7507P)

THROUGH : Donna Judkins, Biologist

Brian Anderson , Branch Chief

Environmental Risk Branch 2 Environmental Fate and Effects Division (7507P )

TO: Miguel Zavala, Chemical Review Manager Tracy Perry, Team Leader Kelly Sherman, Branch Chief Risk Management Implementation Branch 3

Pesticide Re

- evaluation Division (7508P)

The Environmental Fate and E ffects Division (EFED) reviewed comment s from the technical registrant, Syngenta, and from the Physician’s Committee for Responsible Medicine (PCRM) on the “ EFED and AD Registration Review Problem Formulation f or Cyproconazole ” (DP 429082 , Docket ID EPA

- HQ

OPP

- 2015

- 0462 ). The purpose of this memorandum is to respond to th e s e comment s

. The comments are briefly paraphrased below and followed by a response from EFED.

Comments from Syngenta

1. Conclusions from Previous Risk Assessments : EPA conclusion of acute and chronic LOC exceedances for small birds eating short grass is very conservative. The low caloric and nutritive value of short grass makes it unlikely for small birds to rely on it as their sole dietary source. The unlikely occurrence of small birds feeding exclusively on short grass is specifically highlighted in

the US EPA T

- REX v1.5.1 Manual Section 4.1.

Estimates of acute and chronic exposure for avian species associated with the use of cyproconazol e can be refined. For example, US EPA (2012) previously used a foliar dissipation half

- life (DT50) of 11.9 days in a Memorandum entitled (“Analysis of Cyproconazole Avian Risk Assessment for Proposed Turf Use” [PC Code 128993; DP Barcode 403335; Date Octob er 25, 2012). Syngenta conceptually agrees with the aforementioned approach for refining the foliar DT50 value of2 cyproconazole and believes that the available weight

- of

- evidence supports use of a DT50 value of 11.9 days in future cyproconazole ecological risk assessments for terrestrial animals.

EFED Response: The cited section of the Problem Formulation reiterates conclusions presented in previous assessments. A new assessment will be conducted for Regis tration Review. Refinements

identified in the cited 2012 memo will be used unless new information suggests that they are no longer applicable.

2. Chronic Daphnid Endpoint : Syngenta believes that the endpoint for MRID No. 43187701 (NOAEC=0.29 ppm) should be used for risk assessment rather than the endpoint for MRID No. 47036201 (NOAEC=0.019 ppm) . Syngenta is aware of three Daphnia chronic studies ( MRID No. 43187701 and MRID No. 47036201; as well as Jenkins et al. 1989, which can be provided to the EPA upon request). T he NOAEC for MRID No. 47036201 of 0.019 m g ai/L is >15

- fold lower than the endpoint for MRID No. 43187701 and >3

- fold lower than the endpoint for Jenkins et al. (1989). Calculations from the US ECOSAR modeling tool provide additional evidence that the endpoint reported in MRID No. 43187701 more a ccurately represents the threshold of biological effect.

EFED Response: EFED’s policy is to use the lowest endpoint from studies classified as acceptable or supplemental/quantitative for each taxon.

3. Chronic Mysid ACR Calculation : As previously commented , Syngenta believes that the collective weight of evidence provides strong support for use of data from MRID No. 43187701 in ecological risk assessments of cyproconazole. Therefore, the ACR for mysid shrimp should be calculated using

the NOAEC from that st udy.

EFED Response: The EFED Problem Formulation recommends that a chronic mysid toxicity study be requested as part of Registration Review to remove the uncertainty inherent in the use of an ACR.

4. Avian Reproduction MRID : Syngenta wants to bring a typo t o the attention of the Agency concerning data evaluation for MRID No. 47340801 to avoid potential confusion in the future. In the

Memorandum entitled “Transmittal of the Data Evaluation Record for MRID 43287701” dated January 23, 2014; PC Code: 128993; DP Barcode: 47739, the MRID No. is incorrectly stated. As noted in the Memorandum, this specific DER pertains to the Frey et al. (2007) study, which is MRID No. 47340801. The full DER report has the correct MRID listed and the error appears limited to only

th e Memorandum transmittal.

EFED Response: EFED acknowledges that the MRID is incorrect in the referenced DER transmittal

memo.

5. Avian Reproduction Endpoint: Syngenta believes that the cyproconazole NOAEC for mallard duck is 16.4 mg/kg

- diet, as reported in the original study report (MRID No. 47340801). This conclusion is based on biological relevance and is further supported by MCnest modeling. The cyproconazole problem formulation describes the chronic avian LOAEC based on live embryos/viable embryos (LE/VE ) as 10.9 mg/kg

- diet due to a 2.4% reduction. While EPA’s subsequent statistical analysis in the data evaluation record (US EPA 2014) concluded that this effect was significant, Syngenta believes that it is not biologically relevant, rather it is due to a statistical manifestation rather than dose dependent effect associated with exposure to cyproconazole. In addition, Syngenta notes that such a small effect would not culminate in a population

- level effect as demonstrated by MCnest model simulations.3 EFED Response: EFED continues to believe that the conclusions presented in the DER for MRID

47340801 are valid

. EFED expects to continue to use the MCnest model for assessment of risks to birds during Registration Review for cyproconazole and will carefull y evaluate the results from the modeling.

6. Endangered Species Assessment: Simple deterministic screening level assessments, which are highly conservative by design, can facilitate rapid initial screening/exclusion criteria for a pesticide active ingredient s’ 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 endang ered (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. If, however, an RQ is generated that exceed s 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 (fa lsely 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 m odelling and assessment analysis, and other pertinent species

- specific and pesticide

- specific data.

EFED Response: EFED’s methodology for assessing risk to listed species is under development, as

described in Section 8.4 of the Problem Formulation.

7. Poll inator Studies: Syngenta notes that exposure of terrestrial invertebrates to pesticides alone does not equate to impact and highlights that ecological risk assessment should both consider and compare exposure and hazard ( i.e. effects) profiles in order to evaluate potential risk.

EFED Response: EFED concurs that consideration of both exposure and hazard profiles is necessary for assessment of risk.

Comments from the Physician’s Committee for Responsible Medicine

1. Acute Passe rine Toxicity Testing: Acute toxicity testing with a passerine species is a data gap for

seven conazole chemicals including cypro conazole. As such, PCRM is requesting that the Agency consider selecting representative conazoles with which to generate test data, thereby reducing the

num ber of overall tests conducted. Additionally, PCRM recommends that the OECD Test Guideline 223, Avian Acute Oral Toxicity Test be used as the protocol instead of the EPA Guideline 850.2100 in an effort to potentially reduce th e number of animals tested.

EFED Response: EFED appreciates the comment from PCRM. PCRM’s comment was considered by EFED’s Terrestrial Technical Team (TTT). In regard to PCRM’s comment about selecting representative chemical(s)/data to bridge to untested chemicals, EFED considers such an approach when it is appropriate. Based on the limited dataset for the conazoles, results for acute oral toxicity testing with the bobwhite quail vary widely despite similar chemical structures (acute LD 50 s range from 150 to 2,825 mg/kg). Therefore, selection of appropriate chemical(s) to represent the conazoles group as surrogates is difficult and the test is unlikely to capture the broad range of results possible for the conazoles group. Additionally, the known challen ges in conducting acute oral testing with passerines ( i.e ., regurgitation), increase the uncertainty in results and decrease the4 confidence in successfully implementing a bridging approach to use data from one chemical to another. As such, EFED does not recommend using this approach to generate acute oral toxicity data with passerines. With regard to the use of OECD TG 223 as the test protocol, current EFED guidance states that species other than bobwhite quail may be used if low background mortality in the laboratory is demonstrated (such that the assumed incidence of random mortality does not depart from the test animal TG 223 background mortality used to validate the protocol for other birds) and regurgitation during the study is not observed (see guid ance document for complete description of terms and criteria) [1]

.

[1] Guidance for Classifying Studies Conducted Using the OECD Test Guideline 223 (TG223) (Acute Avian Oral Sequential Dose Study). Memorandum from D. Brady, November 9, 2011. Available at: https://www.epa.gov/pesticide

- science

- and

assessing

- pesticide

- risks/guidance

- classifying

- studies

- conducted

- using

- oecd [accessed April 25, 2016].