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 the 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 listed species based on the recommendations of the 

April 2013 National Academy of Sciences (NAS) report. 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/catalog.php?record_id=18344, outlines 

recommendations on specific scientific and technical issues related to the development of 

pesticide risk assessments that are compliant with the Endangered Species Act and the Federal 

Insecticide, Fungicide, and Rodenticide Act. In November, the EPA, along with the U.S. Fish & 

Wildlife Service (USFWS), the National Marine Fisheries Service (NMFS) (collectively, the 

Services), and the U.S. Department of Agriculture (USDA), released a summary of their joint 

Interim Approaches for assessing risks to listed species from pesticides. The 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 EPA and the Services. 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 December 2013 PPDC and SFIREG meetings, allowing 

additional opportunities for stakeholders 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 approaches 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 contained in the 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,” dated November 1, 2013, available at 

http://www.epa.gov/espp/2013/nas.html. 

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

consultation with the Services immediately after the workplan is finalized: 

Regarding CBD’s request for EPA to begin informal 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 identify the appropriate time for initiation of 

consultation, either formal or informal, with the Services. The stakeholder engagement paper, 

jointly developed by the EPA, USDA, and the Services and available at 

http://www.regulations.gov/#!documentDetail;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 consultation may result in refinements to 

EPA’s effects determinations that can improve the efficiency of the ESA compliance process. 

For example, EPA may involve the Services at the earliest stages of registration review. In 
3 

general, EPA plans to initiate formal ESA consultation, 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 determinations, EPA will also need accurate 

spatial data regarding the use of pesticides. Each year, approximately 2.8 million pounds of 

captan active ingredient are applied to approximately 1.5 million acres of agricultural land. Thus, 

it should be possible to determine where areas of geographic overlap between 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 200916 

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 information 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 for 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 the 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 studies 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 blackbirds at 100 mg/kg body weight.3” 

EPA Response: The endpoints for avian acute oral and dietary toxicity cited by the Physicians 

Committee for Responsible Medicine are non-definitive (i.e., LD50 > highest dose or 

concentration tested). The highest doses or concentrations tested are not ≥10x of the highest 

avian estimated environmental concentrations (EECs) 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 

assessment4

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

assessment5

, 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 endpoints6

, if there are 

sublethal effects noted in studies, and the 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 will be assumed since risk cannot be precluded. 

Comment: “If this data is not accepted by the Agency 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 reducing the numbers of animals used by up to 61%7. We 

also refer the registrant to the “Guidance for 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) (Acute 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 Section 24(c) Special Local Need for the Use of Captan on 

Strawberries in Florida. Environmental Fate and Effects Division. Office of Pesticide Programs. May 16, 2012. 6

http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/endangered_species_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_guidance/team_authors/terrestrial_biology_tech_team/review_av

ian_acute_oral_oecd_tg223.htm
5 

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 the criteria cited in the guidance for classifying a 

study based on OECD Test Guideline 223 as “acceptable” is that study is conducted using 

bobwhite quail. The EFED guidance further states that “other test species may be acceptable if 

they have low background mortality 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 below; please note that the background mortality 

data for the species in question should be available 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 (freshwater fish) growth and survival was affected at 

doses between 16.5 and 39.6 μg/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, which are from an open literature study9

, in Section 5.1 

of the problem formulation but noted that a formal review of the study conducted in accordance 

with current guidelines for evaluating ecological toxicity data in the open literature10 resulted in a 

study classification of “qualitative” for use in the registration review ecological risk assessment 

due to significant uncertainty associated with exposure concentrations which varied greatly over 

the study. However, the EFED problem formulation also noted that although the fish early-life 

stage toxicity test is considered a data gap due to the lack of an “acceptable” study, fulfilling this 

data requirement has a low potential to add value to the assessment since repeating the study is 

likely to yield the same uncertainty with respect to exposure concentrations. Therefore, the 

Agency does not anticipate including the fish early-life stage toxicity test 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 Toxicity (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) Honey 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_guidance/team_authors/endangered_species_reregistration_work

group/esa_evaluation_open_literature.htm
6 

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 reviewed and categorized as acceptable for risk 

assessment. The CTF understands that the new 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 metabolism 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 understanding, 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 Anaerobic 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 soil 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 this category (one for upland game species and 

one for waterfowl species) have been reviewed and deemed acceptable by the Agency. The 

estimated LD50 values from these studies were >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 the 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 determination 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, substantially 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 weight 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 toxicity 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 testing on vertebrate species in the interests 

of animal welfare concerns.” 

Response: If a passerine acute oral toxicity study yields a definitive, lower LD50 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 

LD50 value for captan, a definitive LD50 for an upland game species (i.e., bobwhite quail) may be 

attainable by testing at higher concentrations given the sublethal effects noted in the original 

study at the highest test concentration; a definitive LD50 would allow the Agency to 

quantitatively estimate risk to birds from acute oral exposure. The CTF would need to provide 

evidence that practical issues 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 exposure concentrations (EECs) from previous 

assessments that are similar to or exceed these values. At this time, the 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, LC50 values in the range of two times higher 

are needed to clear the worst case standard avian acute dosebased assessment for the most 

conservative food item (short-grass). Given the 30% mortality at the highest 

concentration in the quail study, it can be assumed that a resultant definitive LC50 value 

for this species will not be significantly more than the non-definitive LC50 that has been 

determined. Thus, the CTF does not believe a repeat of this test to determine a definitive 

LC50 value will add significant value to the assessment. 

 In addition, the CTF is committed to minimizing testing to vertebrate species in the 

interests of animal welfare concerns. 

Response: Although it may be assumed that a resultant definitive LC50 value for bobwhite quail 

will not be significantly more than the non-definitive LC50, the current available data provide no 

information about the slope of the concentration-response curve and thus cannot be used to 

estimate the LC50. A definitive LC50 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 Validation (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 Eligibility 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 validated methods in water that have served to characterize the 

behavior of this molecule water for many tests. 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 data and summarize this methodology report. This report will 

demonstrate that the methodology in water is adequate for the purposes of fulfilling the ILV. 

Response: EFED is receptive to an alternative 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 formulation 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 were and what role captan 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 contact (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 conducted specifically to assess the potential 

effects of Captan applications during bloom on brood development of honey bees, Apis 

mellifera, under field conditions in central 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 conditions 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 honey 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 captan 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 submitted in lieu of the non-guideline larval honey 

bee oral toxicity test should consider maximum exposure scenarios for registered uses of captan.