2 1. Comments from the Center for Biological Diversity (CBD)

To address comments related to the NAS implementation plan:

EPA has reviewed the comments from CBD on th e registration review docket openings for captan and plans to address many of the concerns raised by CBD as part of the implementation plan for assessing the risks of pesticides to li sted species based on the recommendations of the April 2013 National Academy of Sciences (NAS) re port. EPA will address concerns specific to captan in connection with the development of its registration review decision for captan.

The NAS report, available at http://www.nap.edu/cat alog.php?record_id=18344 , outlines recommendations on specific scientific and tech nical issues related to the development of pesticide risk assessments that are compliant w ith the Endangered Species Act and the Federal Insecticide, Fungicide, and Roden ticide Act. In November, the EP A, along with the U.S. Fish & Wildlife Service (USFWS), the National Marine Fisheries Service (NMFS) (collectively, the Services), and the U.S. Department of Agricultu re (USDA), released a summary of their joint Interim Approaches for assessing risks to li sted species from pesticides. The Interim Approaches were developed jointly by the Agen cies 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 EPA and the Se rvices. The joint Interim Approaches were released prior to the stakeholder workshop held on November 15, 2013. EPA is presenting the joint Interim Approaches at the Decembe r 2013 PPDC and SFIREG meetings, allowing additional opportunities for stake holders to comment on the Interim Approaches. The Agencies will consider public comments on the Interim Approaches prior to implementing them. The Agencies intend to jointly implement these appro aches as part of a phased iterative process. EPA will refine its listed species risk assessments based on these interim approaches. The details of the joint Interim Approaches are containe d in the white paper “Interim Approaches for National-Level Pesticide Endangered Species Ac t Assessments Based on the Recommendations of the National Academy of Sciences April 2013 Report,” dated November 1, 2013, available at http://www.epa.gov/espp/2013/nas.html

.

To address comments from CBD regarding th eir request for EPA to begin informal

consultation with the Services immedi ately after the workplan is finalized:

Regarding CBD’s request for EPA to begin inform al consultation with the Services immediately after the workplan for cpatan is finalized, EPA plans to follow the March 2013 stakeholder engagement paper (“Enhancing Stakeholder Input in the Pesticide Registration Review and ESA Consultation Processes and Development of Economically and Technologically Feasible Reasonable and Prudent Alternatives”) to iden tify the appropriate time for initiation of consultation, either formal or informal, with the Services. Th e stakeholder engagement paper, jointly developed by the EPA, USDA, and the Services and available at http://www.regulations.gov/#!docum entDetail;D=EPA-HQ-OPP-2012-0442-0038 , allows for early interaction with the Services under informal consultation. EPA and the Services acknowledge that early interaction as part of informal consultati on may result in refinements to EPA’s effects determinations that can improve th e efficiency of the ESA compliance process. For example, EPA may involve the Services at th e earliest stages of registration review. In3 general, EPA plans to initiate formal ESA consulta tion, if necessary, at the final decision stage in the registration review process. Consulting later in the process allows the EPA to develop more refined ecological risk assessments and to engage stakeholders in discussions that should result in more focused consultation packages that may include risk mitigation for listed species.

Comment: To make scientifically valid effects de terminations, EPA will also need accurate spatial data regarding the use of pesticides . Each year, approximately 2.8 million pounds of captan active ingredient are app lied to approximately 1.5 million acres of agricu ltural land. Thus, it should be possible to determine where areas of geographic overlap betw een species and captan usage occur. As shown in Figure Two, the U. S. Geological Survey has compiled detailed information regarding captan as part of its National Pesticide Synthesis Project.

Figure Two. Estimated Agriculture Use for Captan in 2009 16

16 USGS Pesticide National Synthesis Project. http://water.usgs.gov/nawqa/pnsp/usage/maps/show_map.php?year=2009&map=CAPTAN&hilo=L

Response: The Agency appreciates the informati on submitted by CBD regarding the spatial extent of agricultural use of captan. EPA will consider this information during the registration

review.

2. Comments from the Physicians Committee for Responsible Medicine

Comment: “It has been well documented that Captan is practically nontoxic to birds. An EPA document from 2004 provides data for avian acute oral toxicity data using game birds as well as avian dietary toxicity data fo r both game birds and waterfowl. 1

In addition, we found data for the avian acute oral toxicity data request: “The LD50 is greater than 5000 mg/kg in mallard ducks [waterfowl] and pheasants [upland game birds]. The LD50 is 2000 to 4000 mg/kg in bobwhite quail.” 2

1 EPA. (2004). Amendment to th e 1994 Captan RED. Document accessed on August 22, 2013 at http://www.epa.gov/oppsrrd1/REDs/0120red.pdf

.4 With respect to the Avian Dietary Toxicity st udies we found data from the National Pesticide Information Center which found that, “Captan is practically non-toxic to slightly toxic to Northern bobwhite quail and mallard on both acute and subacute dietary basis. The acute LD50s are >2000 mg/kg and the subacute dietary LC50s are >2400 ppm feed. Captan is non-toxic to starlings or red-Winged blac kbirds at 100 mg/kg body weight. 3 ”

EPA Response: The endpoints for avian acute oral and di etary toxicity cited by the Physicians Committee for Responsible Medicine are non-definitive ( i.e. , LD 50 > highest dose or concentration tested). The highest do ses or concentrati ons tested are not ≥ 10x of the highest avian estimated environmental concentrations (EEC s) calculated in the most recent assessments ( i.e ., 4968 mg/kg-bw and 5112 mg/kg-diet in the 2007 California red-legged frog litigation

assessment 4 ; 6107 mg/kg-bw and 5112 mg/kg-diet in the 2012 Section 24(c) Special Local Need

assessment 5 , DP 400401), and sublethal effects including weight loss, ataxia, and tremors were noted in some of the studies ( e.g. , MRID 00151236 = GS0120-045 and MRID 00160000 = GS9999-001). Based on EFED’s guidance for using non-definitive endpoints 6 , if there are sublethal effects noted in studies, and th e highest concentration tested is not ≥ 10x of environmentally relevant concentrations ( i.e. , EECs), requesting additional toxicity data to establish a definitive endpoint is recommended. If data are not available for the risk assessment, risk to birds from acute exposure to captan wi ll be assumed since risk cannot be precluded

.

Comment: “If this data is not accepted by the Ag ency then we recommend that OECD Test Guideline 223, Avian Acute Oral Toxicity Test , be used as the protocol instead of EPA

Guideline 850.2100 in the interest of reduci ng the numbers of animals used by up to 61% 7 . We also refer the registrant to the “Guidance fo r Classifying Studies Conducted Using the OECD Test Guideline 223 (TG223) (Acute Avian Oral Sequential Dose Study)” available on the Agency’s website.”

Response: EFED concurs that the “Guidance for Classifying Studies Conducted Using the OECD Test Guideline 223 (TG223) (Acu te Avian Oral Sequential Dose Study)” 8 should be

2 Extoxnet. (1996). Website accessed on August 22, 2013 at http://extoxnet.orst.edu/pips/captan.htm

. 3 National Pesticide Information Center. (2000). Captan : Technical Fact Sheet. Website accessed on August 22,

2013 at http://npic.orst.edu/factsheets/captantech.pdf

4 Risks of Captan Use to Federally Threatened California Red-legged Frog ( Rana aurora draytonii ). Pesticide

Effects Determination. Environmental Fate and Effects Division. Office of Pesticide Programs. October 18, 2007. http://epa.gov/espp/litstatus/effects/redleg-frog/

5 Ecological Risk Assessment in Response to the Sectio n 24(c) Special Local Need for the Use of Captan on

Strawberries in Florida. En vironmental Fate and Effects Division. Office of Pesticide Programs. May 16, 2012.

6
http://www.epa.gov/pesticides/science/efed/policy_guidan ce/team_authors/endangered_s pecies_reregistration_work group/esa_non_definitive_endpoints.htm

7 OECD. (2010). Test Guideline 223: Avian Acute Oral Toxicity Test Method. OECD Guidelines for the Testing of Chemicals. Website accessed on August 31, 2012 at http://lysander.sourceoecd.org/vl=3006812/cl=16/nw=1/rpsv/ij/oecdjournals/1607310x/v1n2/s33/p1

. 8

http://www.epa.gov/pesticides/science/efed/policy_guidan ce/team_authors/terrestrial_biology_tech_team/review_av ian_acute_oral_oecd_tg223.htm5 consulted if the registrant intends to submit an avian acute oral study based on OECD Test

Guideline 223. It should be noted that one of th e criteria cited in the guidance for classifying a study based on OECD Test Guideline 223 as “ac ceptable” is that st udy is conducted using bobwhite quail. The EFED guidance further states th at “other test species may be acceptable if they have low background mortalit y in the laboratory and do not regurgitate during the study; however, if a species other than bobwhite quail is used, the study should be reviewed by the Terrestrial Biology Tech Team (TBTT) - see be low; please note that the background mortality data for the species in question should be ava ilable from the submitting laboratory at the time of

the TBTT review.”

Comment: “Finally, would like to comment on the fish early-life stage toxicity test. A full lifecycle study indicated that fathead minnow (freshwate r fish) growth and survival was affected at

doses between 16.5 and 39.6 μ g/L.5. The Agency likely has these data and we recommended considering whether it can be used in place of the early-life stage test.”

Response: The Agency cited these data, whic h are from an open literature study 9 , in Section 5.1 of the problem formulation but noted that a form al review of the study co nducted in accordance with current guidelines for evaluating ecologi cal toxicity data in the open literature 10 resulted in a study classification of “qualitative” for use in th e registration review eco logical risk assessment due to significant uncertainty associated with exposure concentrations wh ich varied greatly over the study. However, the EFED problem formulati on also noted that alt hough the fish early-life stage toxicity test is consider ed a data gap due to the lack of an “acceptable” study, fulfilling this data requirement has a low potential to add valu e to the assessment since repeating the study is likely to yield the same uncertainty with respec t to exposure concentrations. Therefore, the Agency does not anticipate including the fish ea rly-life stage toxicity te st in the registration review Data Call-In for captan.

3. Comments from the Captan Task Force (CTF)

Comment: CTF will address the following environmental fate and ecological effects data gaps if requested in the Data Call-In:

 835.4100 Aerobic Soil Metabolism

 835.4400 Anaerobic Aquatic Metabolism

 850.2100 Avian Acute Oral Toxici ty (passerine species)

 850.4100 Seedling Emergence and Seedling Growth

 850.4150 Vegetative Vigor

 850.4500 Aquatic Plant Growth (aquatic non-vascular plant toxicity)

 Non-GDLN (Special study) Hone y Bee-Oral Toxicity (Adult)

9 E000945 (MRID 00057846). Hermanutz, R.O., Mueller, L. H., Kemper, K.D. 1973. Effects Captan toxicity to fathead minnows ( Pimephales promelas ), bluegills ( Lepomis macrochirus ), and brook trout ( Salvelinus fontinalis ).

J. Fish. Res. Board. Can. 30: 1811-1817.

10
http://www.epa.gov/pesticides/science/efed/policy_guidan ce/team_authors/endangered_s pecies_reregistration_work group/esa_evaluation_open_literature.htm6 Response: The Agency appreciates this clarification regarding the CTF’s intention to address these data gaps.

Comment: 835.4200 Anaerobic Soil Metabolism – “The EPA Problem Formulation indicates that the Anaerobic Soil Metabolism requirement is partially fulfilled with the two existing

anaerobic soil metabolism studies that were re viewed and categorized as acceptable for risk

assessment. The CTF understands that the ne w guideline (835.4200 Anaerobic Soil Metabolism) suggests a total of four soils to better define the rate of transformation for a chemical. However, the EPA suggested that the need for the two additional soils was because OCSPP uses an upper 90th percentile estimate of soil metabolism half -lives for modeling purposes related to the exposure assessment. The CTF’s understanding is that if anaerobic aquatic metabolism data is available, the anaerobic soil me tabolism data is not used in aquatic exposure modeling. The CTF will submit an anaerobic aquatic metabolism study which evaluated the metabolism in two aquatic sediment systems. According to our unde rstanding, halflives from the anaerobic aquatic metabolism study would be the primary input in aquatic exposure modeling assessment. This would make the requirement to generate data on anaerobic soil metabolism on two additional soils of limited value to the assessment. Thus, the CTF would request that the requirement for anaerobic soil metabolism (835.4200 Anaer obic Soil Metabolism) be waived.”

Response: The Agency concurs with the CTF. However, the anaerobic aquatic metabolism studies must be reviewed by EPA and found to be acceptable for risk assessment purposes before the Agency can determine that the anaerobic so il metabolism study is no longer needed for registration review.

Comment: 850.2100 Avian Acute Oral Toxicity ( upland game or waterfowl species) – “The two submitted Avian Acute Oral Toxicity studies for th is category (one for upland game species and one for waterfowl species) have been review ed and deemed acceptable by the Agency. The

estimated LD50 values from these studies we re >2150 and >2000 mg/kg-bw for the Bobwhite quail and Mallard duck, respectively. As the Agency indicates, a data gap does not exist for this requirement. However, the Agency is suggesting a study to generate a definitive LD50 value. The reasoning for this request is related to th e lack of a definitive LD50 value in relation to estimated exposure concentrations (EECs) from previous assessments that exceed these values. At this time, the CTF does not feel that dete rmination of a definitive LD50 value will add significant value to the assessment for the following reasons:

 If the EEC values from previous assessments are representative of values determined in the Registration Review risk assessment, subs tantially higher LD50 values will be needed

to clear the standard avian acute dose-based assessment for the most conservative food item (short-grass) and the smallest body wei ght category, 20 g (i.e., the worst case).

Given that sublethal effects were noted in the original studies at the higher test concentrations, it is unlikely that any resultant definitive LD50 value determined from a study with either species will be high enough to pass the assessment and add significant

value to the assessment.

 Practical issues can be encountered with effectively dosing birds at doses beyond the limit dose (2000 mg/kg-bw), especially if capsule dosing is required.7  A passerine acute oral toxici ty study has been requested and may possibly determine a definitive, lower LD50 value for captan, which would then drive the acute avian

assessment.

 Finally, the CTF is committed to minimizing tes ting on vertebrate species in the interests

of animal welfare concerns.”

Response: If a passerine acute oral toxicity study yields a definitive, lower LD 50 value for captan, then that endpoint would be used to estimate risk to birds from acute dose-based exposure to captan. If a passerine acute oral toxicity study does not yield a definitive, lower

LD 50 value for captan, a definitive LD 50 for an upland game species ( i.e. , bobwhite quail) may be attainable by testing at higher co ncentrations given the sublethal effects noted in the original study at the highest test c oncentration; a definitive LD 50 would allow the Agency to quantitatively estimate risk to birds from acute oral exposure. The CTF would need to provide evidence that practical issu es prevent testing at doses beyond the limit dose ( i.e. , 2000 mg/kgbw).

Comment: 850.2200 Avian Dietary Toxicity ( upland game and waterfowl species ) – The two submitted studies (one for upland game species and one for waterfowl species) for this category have been reviewed and deemed acceptable by the Agency. The estimated LC50 values from these studies were 4680 mg/kg-diet, corrected for % a.i. (>5200 mg/kg-diet not corrected for a.i.) for both the Bobwhite quail and Mallard duck. As the Agency indicates, a data gap does not exist for this requirement. However, the Agency is suggesting the conduct of additional studies to generate a definitive LC50 value. The reasoning for this request is based on the lack of a

definitive LC50 value in relation to estimated ex posure concentrations (EECs) from previous

assessments that are similar to or exceed these values. At this time, th e CTF does not feel that determination of a definitive LC50 value add significant value to the assessment for the following reasons:

 If the EEC values from previous assessments are representative of values determined in the Registration Review risk assessment, LC 50 values in the range of two times higher

are needed to clear the worst case standard av ian acute dosebased asse ssment for the most conservative food item (short-grass). Give n the 30% mortality at the highest concentration in the quail study, it can be a ssumed that a resultant definitive LC50 value for this species will not be significantly mo re than the non-definitive LC50 that has been determined. Thus, the CTF does not believe a rep eat of this test to determine a definitive LC50 value will add significant value to the assessment.

 In addition, the CTF is committed to minimizi ng testing to vertebra te species in the

interests of animal welfare concerns.

Response: Although it may be assumed that a resultant definitive LC 50 value for bobwhite quail will not be significantly more than the non-definitive LC 50, the current availabl e data provide no information about the slope of the concentration-response curve and thus cannot be used to

estimate the LC 50

. A definitive LC 50 value and associated slope of the concentration-response curve would add significant value to the assessment.8 Comment: 850.6100 Environmental Chemistry Methods (ECM) and Associated Independent Laboratory Validation (ILV) for water

– The CTF understands that under the relevant guidelines, an Independent Laboratory Valida tion (ILV) is required. Captan is a well established chemical, having been first registered in the US under FIFRA in 1951 and having undergone multiple US regulatory reviews since that time (Reregistration Eligib ility Decision, Captan, List A, Case 120; http://www.epa.gov/oppsrrd1/REDs/0120red.pdf ). This chemical has been well characterized from an environmental fate and ecotoxicology perspective, which includes from an aquatic

residue assessment. There exist va lidated methods in water that ha ve served to characterize the behavior of this molecule water for many test s. While a guideline method validation procedure and report are not available, the methods that have been used have been validated by the testing laboratories and have yielded reliable data for tests submitted the Agency. The CTF would propose that in lieu of a separate ILV study, it will review the existing methodology that has already yielded reliable da ta and summarize this methodology report. This report will demonstrate that the methodology in water is ade quate for the purposes of fulfilling the ILV.

Response: EFED is receptive to an a lternative validated method in lieu of an ECM/ILV study for water. However, the submitted method must demonstrate that the methodology for water is adequate to evaluate captan and its major degradates.

Comment: Non-GDLN (special study) Honey Bee-Oral Toxicity (Larvae) – The requirement for this study is based on two factors:

 A single incident involving brood losses and use of captan; and

 The “White Paper in Support of the Proposed Risk Assessment Process for Bees” as submitted to the FIFRA Scientific Advisory Panel which proposes a screening-level risk assessment process that includes an acute oral toxicity test with larval bees. The implication from the information reported in the Captan problem fo rmulation is that a single incident involving honey bee brood losses and captan has been reported. It is not

known what the circumstances of the incident we re and what role capt an played in the brood losses and if this was a result of typical use or misuse of the product. However, the lack of reported data linking captan to honey bee issues is not surprising given the low toxicity of Captan to honey bees as demonstrated in c ontact (LD50 >200 ug a.i./bee) and oral (LD50 > 100 ug a.i./bee) toxicity studies. In addition, the referenced white paper indicates that in lieu of a honey bee larval oral toxicity study, the larval toxicity screening

‐ level assessment could be based on a honey bee brood study using in

‐ hive exposure of brood fed by adults. The CTF will submit a peer-reviewed study that was cond ucted specifically to assess the potential effects of Captan applications during bloom on brood development of honey bees, Apis mellifera , under field conditions in cent ral and northern California (Everich, R., C. Shiller, J. Whitehead, M. Beavers, and K. Barrett. 2009. Effects of Captan on Apis mellifera brood development under field conditions in California almond orchards. J. Econ. Entomol. 102(1): 20-29 (2009)). This study determined that Captan was not harmful to foraging adult or larval honey bees under the typical field application c onditions that were evaluated. The CTF feels that this study should fulfill the requirement for a larval brood oral toxicity study as it provides a more realistic assessment of hone y bee brood survival under representative application conditions.9 Response: The CTF is welcome to submit the above-referenced peer-reviewed study that was conducted specifically to assess the potential effects of capta n applications during bloom on brood development of honey bees. The study will be considered by EFED at the time of submission. It should be noted that any study su bmitted in lieu of the non-guideline larval honey bee oral toxicity test should consider maximum exposure scenario s for registered uses of captan.