Docket Number EPA-HQ-OPP-2015-0063 

www .regulations.gov 

Sabadilla Alkaloids Final Work Plan 

Registration Review 

Case Number 3128 

March 2016 

Approved by: 

Director 

Pesticide Re-evaluation Division 

Date: 
INTRODUCTION 

This is the Environmental Protection Agency's (EPA or the Agency) Final Work Plan (FWP) for 

the registration review of sabadilla alkaloids. This work plan addresses public comments 

received concerning the Preliminary Work Plan (PWP), which was posted in the sabadilla 

alkaloids registration review docket (EPA-HQ-OPP-2015-0063). Sabadilla alkaloids is 

registered as an insecticide for the control of thrips on citrus, avocados, and mangos. There are 

no products registered explicitly for non-agricultural (residential) uses. The active ingredient is 

obtained as an extract from the ground seeds of the sabadilla plant. It is a complex mixture, with 

the two primary components being the alkaloids cevadine (crystalline veratrine) and veratridine 

(amorphous veratrine). The remainder of the mixture includes smaller amounts of alkaloids such 

as sabadine, sabadinine, and sabadilline. 

The Agency is implementing the registration review program pursuant to Section 3(g) of the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and will review each registered 

pesticide every 15 years to determine whether it continues to meet the FIFRA standard for 

registration. Changes in science, public policy, and pesticide use practices occur over time. The 

registration review program is intended to make sure that, as the ability to assess risk evolves and 

as policies and practices change, all registered pesticides continue to meet the statutory standard. 

The public phase of registration review begins when the initial docket is opened for each case. 

Information on this program is provided on the Agency's website.

1 

The FWP begins with any updates since the PWP was issued. Next is a summary of substantive 

comments received during the public comment period for the PWP concerning anticipated data 

needs, expected risk assessments, or the estimated timeline identified in the PWP, and a 

summary of the Agency's responses to those comments. This section is followed by registration 

review planned data needs, risk assessments expected to be conducted, and the projected 

registration review timeline for sabadilla alkaloids. Lastly, there is a discussion of next steps. 

UPDATES SINCE THE PWP WAS ISSUED 

There are no updates on sabadilla alkaloids since the PWP, aside from the inclusion in this 

document of some anticipated data requirements inadvertently omitted from the PWP. 

SUMMARY OF COMMENTS AND AGENCY RESPONSES 

During the 60-day public comment period on the Sabadilla Alkaloids Preliminary Work Plan, 

which opened on October 2, 2015 and closed on December 1, 2015, the Agency received two 

public comments. Comments were submitted by FIFRA Endangered Species Taskforce (FESTF) 

and McLaughlin Gormley King Company (MGK). The comments do not address the timeline 

described in the PWP, but they do address the planned ecological and human health risk 

assessments and data requirements. In the PWP, EPA also solicited comments on the specific 

topics of environmental justice, water quality concerns, and trade irritants, but no comments or 

information were received on those issues. 

1 http://www2 .epa.gov/pesticide-reevaluation 

2 
This section does not capture every comment made about the PWP nor all of the Agency's 

responses. No comments resulted in changes to the anticipated registration review data needs, 

risk assessments or timeline. Public comments are located in the public docket. 

Comments submitted by FESTF in EPA-HQ-OPP-2015-0063-0008. 

Comment: FESTF noted that MGK is member of the task force and is entitled to make use of the 

FESTF database on species proximity to use sites. 

Response: The Agency is aware of the data developed by FESTF and will use those data to 

evaluate risks to listed species, as appropriate. 

Comments submitted by MGK in EPA-HQ-OPP-2015-0063-0009. 

Comment: MGK noted the value of sabadilla alkaloids products to organic growers. 

Additionally, the registrant indicated that their intent to develop the data that EPA requires and, 

furthermore, that they express interest in adding additional uses to their products in the future. 

Response: EPA thanks MGK for these comments and will take them into consideration. 

PLANNED DATA NEEDS 

Table 1 below summarizes the planned data needs for sabadilla alkaloids based on the Problem 

Formulation or the Environmental Fate, Ecological Risk, Endangered Species, and Drinking 

Water Assessments for Sabadilla Alkaloids, and the Human Health Assessment Scoping 

Document in Support of Registration Review. The planned data needs have changed from what 

was included in the PWP. The following guideline numbers were inadvertently omitted from the 

PWP however, they have been included in the FWP: 860.1 850, 860.1 900, and 875.2000. 

Table 1: Planned Data Needs for the Sabadilla Alkaloids Registration Review 

Guideline 

Number2 

835 .61 00 

Study Title 

850.10 I 0 Freshwater invertebrate acute toxicity 

Estimated 

Timeframe 

Test Material (Months from 

receipt of DCI) 

TGAl

3 12 

2 On June 27, 20 12, EPA announced certain revisions in harmonized guideline series 850 - Ecological Effects Tests - including 

renumbering and other designations or changes for some guideli ne studies. See ··Final Test Guidelines; OCSPP 850 Series: 

Notice of Availability'" 77 FR 38282, June 27, 2012. hnp://www.regulations.gov/#!documentDetail;D=EPA-HO-OPPT-2009-

0 154-0028 3 TGAI refers to a mixture ofsabadilla alkaloids that would be representative of the acti ve ingredient fou nd in the registered 

product. It has been reported that there is significant variation in the concentrations of individual components of the active 

ingredient among samples of sabadilla alkaloids. As a result, all TGAI should include a confirmation that the material contains 

the same relative proportions of veratridine, cevadine, sabadinine, and sabadine. 

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Table 1: Planned Data Needs for the Sabadilla Alkaloids Registration Review 

Estimated 

Guideline Study Title 

Timeframe 

Number2 Test Material (Months from 

receipt ofDCI) 

850. I 025 Estuarine/marine invertebrate acute toxicity TGAI 12 (eastern oyster is the preferred test species) 

850. I 035 Estuarine/marine invertebrate acute toxicity TGAI 12 (mysid shrimp) 

850.1075 Freshwater fish acute toxicity TGAJ 12 

(cold water and warm water species) 

850.1075 Estuarine/marine fish acute toxicity TGAI 12 

850.1300 Freshwater inve1tebrate life cycle TGAI 12 

850.1350 Estuarine/marine inve11ebrate life cycle TGAI 12 

850.1400 Freshwater fish early-life stage TGAI (cold water or warm water species, using the 12 

same species as GDL# 850. l 075) 

850.1400 Estuarine/marine fish early-life stage TGAI 12 

Whole sediment: invertebrates subchronic: 

850.1735 freshwater amphipod, Hyalella azteca, and TGAI 12 

midge, Chironomus dilutus 

Whole sediment invertebrates subchronic: 

850.1740 Estuarine/marine amphipod, Leptocheirus TGAI 12 

plumulosus 

Non- Whole sediment chronic (testing with the most 

GDLN4 sensitive species identified from the subchronic TGAI 24 

studies) 

850.2 100 Avian acute oral toxicity (bobwhite quail or TGAI 12 mallard duck) 

850.2100 Avian acute oral toxicity (passerine species) TGAI 12 

850.2200 Avian Dietary Toxicity (bobwhite quail and TGAJ 12 mallard duck) 

850.2300 Avian reproduction (bobwhite quail and mallard TGAI 24 

duck) 

4 A tiered testing strategy may be considered for the data recommended to be required for sediment toxicity. Under 

this strategy, I 0-day sediment toxicity testing is first conducted with Hyale/la azteca, Chironomus dilutus, and 

l eptocheirus p/umulosus under OSCPP Guidelines 850.1735 and 850.1740. After submission and review of data 

from these studies (including a comparison of estimated environmental concentrations in sediment and pore water 

with toxicity results from the I 0-day studies), the Agency will advise the registrant on the need for one or more 

chronic sediment toxicity studies 

4 
Table 1: Planned Data Needs for the Sabadilla Alkaloids Registration Review 

Estimated 

Guideline Timeframe 

Number2 Study Title 

Test Material (Months from 

receipt of DCI) 

Non- Honeybee adult acute oral toxicity (Tier I) TGAI 12 Guidelines 

Non- Honeybee adult chronic oral toxicity (Tier I) TGAI 12 Guidelines 

Non- Honeybee larval acute and chronic oral toxicity TGAI 12 Guideline5 (Tier I) 

Non- Nectar and pollen residue study for insect TEP 24 Guideline5 pollinators (Tier II) 

Non- Semi-fi eld testing for honeybees (Tier II) TEP 24 Guideline5 

850.30405 Field testing for pollinators (Tier III) TEP 24 

850.4 100 Seedling emergence (Tier I) TEP 12 

850.4 150 Vegetative vigor (Tier II) TEP 12 

850.4400 Aquatic vascular plant growth (Lemna spp.) TGAI 12 

850.4500 Algal toxic ity (Pseudokirchneriella subcapitata) TGAI 12 

850.4500 Marine diatom (Skeletonema costatum) TGAI 12 

850.4500 Freshwater diatom (Navicula pelliculosa) TGAI 12 

850.4550 Cyanobacterium (Anabaenajl.os-aquae) toxicity TGAI 12 

860.1100 Chemical identity TGAI 6 

860. 1300 Nature of the residue in plants TGAI 24 

860. 1300 Nature of the residue in livestock TGAI 24 

860.1340 Residue analytical methods 

Residues of 24 

concern 

860.1360 Multiresidue method Residues of 24 

concern 

860.1380 Storage stability 

Residues of 24 

concern 

860.1480 Magnitude of the residues-- TGAI or plant 24 meat/mil k/poultry/eggs metabolite(s) 

860.1500 Magnitude of the residues--crop fie ld trials TEP 24 

860.1 520 Magnitude of the residues--processed food/feed TEP 24 

TGAI and 

860. 1650 Submittal of analyt ical reference standards residues of 12 

concern 

860.1850 Confi ned accumulation in rotational crops TEP 24 

860. 1900 Fie ld accumu lation in rotationa l crops TEP 24 

870.3 150 90-day oral, dog TGAI 24 

870.3200 21/28-day dermal TGAl 24 

5 The need for Tier II and Tier III poll inator data is contingent upon the results of the lower tier testing. 

5 
Table 1: Planned Data Needs for the Sabadilla Alkaloids Registration Review 

Estimated 

Guideline Timeframe 

Number Study Title 

Test Material (Months from 

receipt of DCI) 

870.3465 2 1 /28- or 90-day inhalation, rat TGAI 24 

870.3700 Pre-natal developmental toxicity, rabbit TGAI 24 

870.3800 Reproduction, rat TGAI 48 

870.4200 Carcinogenicity, mouse and combined TGAI 48 chronic/carc inogenicity, rat 

870.6200 Neurotoxicity batte1y: acute and subchronic, rat TGAI 12 

870.7485 General metabolism TGAI 24 

870.7800 Immunotoxicity TGAI 12 

875.2000 Background for post application exposure TGAI 24 

monitoring test guidelines 

875.2100 Dislodgeable foliar dissipation TGAI 24 

Planned Data Needs for the Veratridine Component 

835.1230/ Leaching and adsorption/desorption 12 835.1240 

835.2 120 Hydrolysis 12 

835.2240 Aqueous photolysis 12 

835.2410 Soil photolysis 12 

835.4100 Aerobic soil metabolism Veratridine 24 

835.4300 Aerobic aquatic metabolism 24 

835.4400 Anaerobic aquatic metabolism 12 

850.1 730 Accumulation in fish 12 

850.6100 Environmental chemistry methods & independent 24 laboratory validation (soil and water) 

Planned Data Needs for the Cevadine Component 

835.2120 Hydrolysis 12 

835.4 100 Aerobic soil metabolism Cevadine 24 

835.4300 Aerobic aquatic metabolism 24 

TOAi = technical grade active ingredient; TEP = typical end-use product 

RISK ASSESSMENTS FOR REGISTRATION REVIEW 

During registration review, the Agency will conduct a comprehensive ecological risk assessment, 

including an endangered species assessment, for all uses of sabadilla alkaloids. For human 

health, EPA will conduct revised dietary, residential, and occupational risk assessments during 

registration review. If toxicological endpoints or points of departure are revised based on the 

data that are required for registration review, they will be considered in the new assessments, as 

will any changes to the standard operating procedures or default exposure assumptions. 

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Table 2 below summarizes the planned registration review risk assessments based on the EFED 

Problem Formulation and the HED Scoping Document. The planned assessments have not 

changed from what was included in the PWP. 

Table 2: Planned Risk Assessments for the Sabadilla Alkaloids Registration Review 

Type of Risk Assessment 

Comprehensive ecological 

(species to be assessed 

include terrestrial and aquatic 

organisms), including 

endangered s ec1es 

Incidents 

Conduct? Notes 

The Agency will conduct a comprehensive 

ecological assessment including an endangered 

Y species assessment. Species to be assessed include 

terrestrial and aquatic organisms. 

Will check for There were no reported ecological incidents for 

updates sabadilla alkaloids. See page 13 of the Problem 

Formulation for additional information. 

~~~~~~gz~ii] ~~~ 

Drinking water 

Occu ational 

Handlers (mixers, loaders, 

applicators) 

Y The dietary risk assessment may be revisited, as 

needed, to reflect new data and current policy. 

Y Drinking water will be reevaluated as part of 

registration review. 

y 

t--~~~~~~~~~~ +-~~~~~---1 

Occupational handler and post-application dermal and 

inhalation assessments will be revisited to reflect all 

potential exposure scenarios, updated policies, and 

Post-a lication y 

Residential 

Handlers N 

Post-application 

N 

Other 

Aggregate y 

Cumulative N 

new data. 

The label does not prohibit the use of sabadilla 

alkaloids in residential settings, but given the uses are 

citrus, avocado, and mango, it does not appear that a 

residential handler assessment will be needed. 

A conventional residential post-application 

assessment is not needed. The need for drift and 

volatility assessments will be considered during 

reaistration review. 

As needed to reflect new data and current policy, for 

a re atin food and drinkin water ex osures. 

Sabadilla alkaloids have not been identified as a 

member of a cumulative group that shares a common 

mechanism of toxicit . 

7 
Tolerances y New data anticipated to be required will be used to 

establish tolerances as necessary. 

Incidents Will check for There were three incidents reported and classified as 

updates minor severity. For a discussion of reported human 

incidents for sabadilla alkaloids, see page 2 of the 

Sabadilla alkaloids: Tier I (Scoping) Review of 

Human Incidents. 

TIMELINE 

EPA has created the following estimated timeline for the completion of the sabadilla alkaloids 

registration review in Table 3 below. The projected timeline has been updated to reflect impacts 

of public comments received, changes to the planned data needs, and/or recent actions. 

Table 3: Registration Review for Sabadilla Alkaloids - Projected Registration Review 

Timeline 

Activities Estimated Date 

Opening the Docket 

Open Docket and 60-day Public Comment Period 2015 October 

(completed) 

Close Public Comment 2015 December 

(completed) 

Case Development 

Final Work Plan 2016 March 

Issue DCI 2016 April-June 

Data Submission 2020 April-June 

60-day Public Comment Period for Draft Risk Assessments6 2021 OctoberDecember 

Registration Review Decision 

60-day Public Comment Period for Proposed Registration Review 2022 JulyDecision September 

Registration Review Decision and Begin Post-Decision Follow-up 2022 

Total (years) 7 

NEXT STEPS 

Based on the schedule above, which includes standard timeframes for data development and the 

public process for registration review, the projected date for completing the sabadilla alkaloids 

registration review comes close to the deadline for completing all registration reviews by 

October 1, 2022. The Agency will work with the registrant to develop an expedited plan for 

registration review. 

6 The regulations governing Registration Review generally require the Agency to provide a public comment period 

of at least 30 calendar days for draft risk assessments; see 40 CFR Part 155.53(c). For conventional pesticides, the 

Agency plans to provide a 60 calendar day public comment period generally for draft risk assessments. 

8 
As noted previously, the Agency plans to require environmental fate, ecological effects, and 

human health (residue, exposure, and toxicology) data for sabadilla alkaloids through a Data 

Call-In Notice, expected to be issued April-June 2016. 

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