UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

MEMORANDUM 

Date: September 21 , 2015 

SUBJECT: Sabadilla Alkaloids: Human Health Assessment Scoping Document in Support of 

Registration Review. 

PC Code: 002201 

Decision No.: 506017 

Petition No.: NA 

DP Bar code: D427827 

Registration No.: NA 

Regulatory Action: Registration Review 

Risk Assessment Type: NA Case No.: 3128 

TXRNo.: NA CAS No.: 8051-02-3 

MRID No.: NA 40 CFR: 170.240 

FROM: o~,~ Karlyn Middleton, M.S., Risk Assessor/Toxicologist 

Zaida Figueroa, DrPH, Industrial Hygienist ~"-'-"'"~"r 

Michael A. Doherty, Ph.D., Chemist 'J::.'"'/ 

Risk Assessment Branch II , 0 "J -

Health Effects Division (7509P) 

THROUGH: Chr

Risk 

istina 

Assessment 

Swartz, 

Branch 

Branch 

II 

Chief ~ 

--~~~~~---- Dan a Vogel, Director ~ 

Jess Rowland, Deputy Director ~-~ 

Health Effects Division (7509P) 

Office of Pesticide Programs 

TO: Roy Johnson, Chemical Review Manager 

Risk Management and Implementation Branch V (RMIB V) 

Pesticide Re-Evaluation Division (7508P) 

Attached is the Health Effects Division's (HED) human health assessment scoping document for 

sabadilla alkaloids to support registration review. 

Page 1 of 13 
Executive Summary 

The Health Effects Division (HED) has evaluated the available data, exposure information, and 

the most recent human health risk assessment for sabadilla alkaloids (Reregistration Eligibility 

Decision (RED), 2004). HED performed this evaluation in order to determine the scope of work 

necessary to support the tolerance exemption and existing registrations. The primary source of 

information for this evaluation was the RED; Special Review and Reregistration Division 

(SRRD), 2004) and the Summary of Toxicology Data from the California Environmental 

Protection Agency (CALEPA, 2001). 

Sabadilla alkaloids are insecticides used for the control of thrips on citrus, avocados, and 

mangos. The alkaloids are obtained as an extract from the ground seeds from the sabadilla plant, 

with the primary insecticidal component being veratrine (CAS No. 8051-02-3), consisting of a 

complex mixture, with the two primary alkaloids being cevadine (crystalline veratrine) and 

veratridine (amorphous veratrine), according to the Merck Index. Sabadilla alkaloids act as 

sodium channel agonists in the nervous system of insects, resulting in persistent neuroexcitation. 

During the evaluation of the sabadilla alkaloids for registration review, HED identified 

significant data gaps. As a result, the Agency met with the registrant to discuss the missing data. 

The registrant indicated to the Agency their intent to submit a full database for review to support 

registration of the sabadilla alkaloids. Therefore, the scoping document provides guidance to the 

registrant regarding the data needed to support the Section 3 registration. 

Hazard ldentificationff oxicology 

The toxicology database for the sabadilla alkaloids is not complete. Several toxicology studies 

are missing per current EPA Part 158 Guidelines ( 40 CFR Part 158). These studies are needed to 

support registration as a conventional pesticide (see appendix A, Table A. l). The available 

studies for the sabadilla alkaloids are limited, and include: acute lethality, oral rat subchronic, rat 

developmental, and mutagenicity studies (Appendix A, Table A.2). Currently, study summaries 

(provided by CAL EPA) are available for the oral rat subchronic and developmental rat toxicity 

studies; however, the full study reports need to be submitted to the Agency for review. 

Depending on the results of the submitted study reports, it may be appropriate to consider 

waivers for certain studies, provided there are adequate justifications for why the studies are not 

needed. 

Toxic effects observed in the available studies for the sabadilla alkaloids include decreased body 

weight and food consumption, effects in the liver and kidney (increased liver weights, and 

elevated AST, ALT and BUN levels), and clinical signs (piloerection, emaciation, polyuria, dark 

crust around the nose, and decreased activity) in oral rat subchronic studies. In rat 

developmental studies, decreased body weight (and body weight gain) was also seen, as well as a 

number of clinical signs (ataxia, decreased activity, abnormal gait, gasping, labored breathing, 

and increased salivation) in maternal animals. Decreased body weight and misaligned and 

unossified sternebrae were observed in fetuses in the presence of comparable maternal effects. 

Therefore, no evidence of increased susceptibility was seen in the rat developmental studies. In 

mice, the only available study is a micronucleus assay in which lethargy and mortality were 

Page 2 of 13 
noted; however, administration of the test substance was via intraperitoneal injection, which is 

not relevant for human exposure, and therefore, the study is of limited utility for the purpose of 

risk assessment. No other studies are available in mice and, no studies are available in dogs or 

rabbits. 

In the last assessment of the sabadilla alkaloids (RED, 2004), endpoints and points of departure 

(PODs) were selected for chronic dietary and dermal and inhalation exposure assessments based 

on the results from a subchronic oral toxicity study in rats. The no observed adverse effects level 

(NOAEL) in the study is 250 mg/kg/day (actual dose of 230 mg/kg/day) based on effects 

(decreased relative liver weights, elevated serum chemistry (BUN), reduced food consumption 

and body weights) observed at the lowest observed adverse effect level (LOAEL) of 500 

mg/kg/day. However, a NOAEL of 11 mg/kg/day was used for risk assessment since an 

adjustment was made to account for purity; the NOAEL was estimated by taking 4.83% (total 

amount of alkaloids in the seed) of the actual dose of230 mg/kg/day (Appendix A, Table A.3). 

Residue Chemistry/Dietary 

The residue chemistry database to support tolerances or exemption from tolerances for residues 

of the sabadilla alkaloids inion food is needed. Studies addressing the nature of the residue in 

plants and livestock are needed, as well as analytical methods suitable for enforcement of the 

residue definition in the target crop commodities. Field trials are needed to determine worstcase residues in target crops and a citrus processing study is needed to determine whether or not 

residues concentrate during processing of citrus into juice, dried pulp, and oil. The residue data 

need to be supported by adequate analytical method and storage stability studies. Based on the 

current uses, rotational crop studies are not be needed because the uses are all on pennanent 

crops. Depending on the outcome of the metabolism studies, field trials, and processing study, a 

feeding study may be necessary to quantify transfer of residues into meat and milk. The 

registrant should thoroughly characterize the test substance used in any residue chemistry 

studies. In addition, any residue data generated in support of the registered uses should reflect 

the currently established use pattern with respect to application rate, pre-harvest interval (PHI), 

application methods and timing. 

The Agency needs several studies in OCSPP Guideline Series 860. The registrant is encouraged 

to consult with the Agency to address questions prior to initiating any residue program. Once 

the studies are received, the Agency will determine the residues of concern for tolerance-setting 

and risk assessment purposes, and as needed, will conduct dietary risk assessments to address 

potential residues in food and drinking water. 

Residential Exposure 

There are no registered residential uses or uses resulting in direct residential exposure associated 

with the sabadilla alkaloids. However, the sabadilla alkaloids can be applied via ground and 

aerial equipment and, therefore, there is the potential for indirect exposure related to spray drift. 

Page 3of13 
Spray Drift and Volatilization 

Residential bystander exposures resulting from off-site transport (e.g., spray drift or 

volatilization) can occur as a result of applications of sabadilla alkaloids. The potential for spray 

drift will be quantitatively evaluated for each pesticide during the registration review process 

and all uses for each pesticide will be considered concurrently. The approach is outlined in the 

revised 2012 Standard Operating Procedures for Residential Risk Assessment- Residential 

Exposure Assessment Standard Operating Procedures Addenda l: Consideration of Spray Drift. 

The Agency has developed a Volatilization Screening Tool and a subsequent Volatilization 

Screening Analysis. During registration review, the Agency will utilize this analysis to 

determine if data (i.e., flux studies, route-specific inhalation toxicological studies) or further 

analyses are needed for sabadilla alkaloids. 

Occupational Exposure 

Sabad ilia alkaloids are insecticides used for the control of thrips on citrus, avocados, and 

mangos. The sole end-use product is formulated as a wettable powder that is mixed with water 

and applied with either aerial or ground equipment. 

Occupational handler and post-application exposures are expected based on the registered 

agricultural uses. Based on the use pattern, occupational exposure from the registered food uses 

is expected to be short-term (1-30 days) and intermediate-term (i.e., 1-6 months) in duration. 

Long-term exposures (i.e., than 6 months) are not anticipated. Maximum single application 

rates previously assessed range from 0.03-0.04 lb ail A for agricultural crops. 

Occupational Handler Exposure 

There is the potential for dermal and inhalation exposure to occupational handlers from the 

currently registered use pattern of sabadilla alkaloids. HED previously conducted ORE 

assessments for the regist~red agricultural uses (SRRD, 2004). HED based the assessments on 

exposure data from the Pesticide Handlers Exposure Database (PHED), assumptions for area 

treated from the Science Advisory Council for Exposure (ExpoSAC) Policy #9, and maximum 

application rates. Handler exposure and risk were calculated at the baseline level of personal 

protection (i.e., long pants, a long-sleeved shirt, no chemical-resistant gloves, and no respirator) 

and with the use of additional personal-protective equipment (PPE) when necessary (e.g., 

chemical-resistant gloves and/or engineering control - enclosed cockpits - for aerial 

applications). Short- and intern1ediate-term occupational handler MOEs were not of concern 

(i.e., MOEs I 00; LOC= lOO) for all registered uses. 

Since the previous review, there have been several updates to HED's exposure policies, 

including updated exposure data for occupational handler assessments and updates to bodyweight assumptions. These assessments will be revised during registration review to reflect 

current Agency policies, data, and assumptions. 

Page 4of13 
Occupational Post-application Exposure 

The previous risk assessments evaluated a number of representative occupational postapplication scenarios based on the registered uses (SRRD, 2004). Per the updated Part 158 data 

requirements (2007), one or more dislodgeable foliar residue (DFR) studies are needed when a 

pesticide has occupational uses that could result in post-application dermal exposure. EPA 

needs the 40CFR DFR data (OCSPP 875.2000 and 875.2100) to facilitate any necessary 

exposure assessment refinements due to changes in toxicological endpoints and to further EPA' s 

general understanding of the availability of dislodgeable foliar pesticide residues for sabadilla 

alkaloids. 

The restricted entry interval (REI) for agricultural occupational exposure is the time period 

following a pesticide application during which entry into the treated area is restricted. The REI 

established for sabadilla alkaloids is 12 hours. Since the RED, there have been several updates 

to HED's exposure policies, including updated exposure data for occupational post-application 

assessments. Occupational post-application assessments will be revised during registration 

review to reflect current Agency policies and to ensure that the REis are adequate to protect 

workers from post-application exposures to sabadilla alkaloids. 

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for sabadilla alkaloids. However, if new policies or procedures 

are put into place, the Agency might revisit the need for a quantitative occupational postapplication inhalation exposure assessment for sabadilla alkaloids during registration review. 

Data Deficiencies, Label Revisions, and Risk Assessment Needs 

Data Needs 

Toxicology 

There are several outstanding toxicity studies for the sabadilla alkaloids, studies which are 

typically needed for registration as a conventional pesticide. Currently, the available toxicity 

studies are limited and include: acute lethality data (which were reviewed by EPA), rat 

subchronic oral and developmental rat toxicity studies, and mutagenicity studies (all reviewed by 

CAL EPA). Provided the available CAL EPA studies are adequate (study reports should be 

provided by the registrant), the studies listed below are required. If the CAL EPA studies are no 

adequate, additional data may be needed. It is possible that some of the studies could be waived 

based on the results of other studies (see Appendix A for specific guideline numbers). Once the 

required studies are submitted, HED will provide updated hazard characterization and endpoint 

selection for dietary and occupational risk assessments; in addition, as needed, an oral endpoint 

will be selected for the purpose of the spray drift assessment. 

Guideline No. Study Description 

870.3150 90 Day Subchronic Dog: a one year dog is only required if the chemical is 

highly bioaccumulating and is eliminated so slowly that it does not achieve 

Page 5of13 
steady state or sufficient tissue concentrations to elicit an effect during a 90-day 

study). EPA would require the appropriate tier II metabolism and 

pharmacokinetic studies to evaluate more precisely bioavailability, half-life, 

and steady state to determine if a longer duration dog toxicity study is needed. 

870.3200 21 or 28 day dermal 

21 /28 or 90 day inhalation: required if there is the likelihood of significant 

repeated inhalation exposure to the pesticide as a gas, vapor, or aerosol. Based 

870.3465 on estimates of the magnitude and duration of human exposure, studies of 

shorter duration, e.g., 21- or 28-days, may be sufficient to satisfy this 

requirement. Registrants should consult with the Agency to determine whether 

studies of shorter duration would meet this requirement.) 

870.3700b Developmental Rabbit 

870.3800 Reproduction Rat 

870.4200 Carcinogenicity Mouse and Combined Chronic/Carcinogenicity Rat 

870.6200 Neurotoxicity Battery: Acute and Subchronic Neurotoxicity 

870.7800 Immunotoxicity 

870.7465 Metabolism and Pharmacokinetics 

Residue Chemistry: 

The following residue studies are required to support the registered uses on citrus, avocado and 

mango; once these data are submitted, HED will determine the need for tolerances, the residues 

of concern for risk assessment and tolerance-setting, and will conduct a dietary exposure 

assessment based on the potential for residues in food and drinking water sources. Note that 

estimated drinking water concentrations will be determined by the Environmental fate and 

Effects Division (EFED), depending on the outcome of any required fate studies. 

Guideline No. Study Description 

860. I I 00 Chemical identity 

860.1650 Submittal of analytical reference standards 

860.1300 Nature of the residue in plants 

860.1300 Nature of the residue in livestock 

860.1340 Residue analytical methods 

860. 1360 Multiresidue method 

860.1380 Storage stability 

Page 6of 13 
Guideline No. Study Description 

860.1500 Crop field trials 

860.1520 Processed food or feed 

860.1480 Meat/milk/poultry/eggs 

Occupational/Residential Exposure: 

HED will conduct updated occupational handler and post-application assessments, based on the 

registered use pattern, and on relevant endpoints and doses for risk assessment. The required 

DFR study will be used to determine post-application dermal exposure and risk. 

• 875.2000, 2100 Dislodgeable Foliar Residue (DFR) Dissipation Study. DFR data are 

required for the registered uses. 

Risk Assessment Needs/Updates 

After receipt of the new toxicology data, HED will consider the appropriateness of the existing 

endpoints based on the new data and current policies and risk assessment methodologies. After 

review of the submitted residue data, HED will set appropriate tolerances as needed. In addition, 

dietary risk assessments will be conducted based on the potential for residues in food and 

drinking water. HED will also conduct revised occupational exposure assessments to reflect the 

use of the most recent exposure data, new toxicity endpoints and PODs, and updated exposure 

inputs. 

Endocrine Disruption 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its most recent registration decision for the sabadilla alkaloids, 

EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment 

scenarios from the existing hazard database. However, as required by FFDCA section 408(p), 

the sabadilla alkaloids are subject to the endocrine screening part of the Endocrine Disruptor 

Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a "naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate." The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 1 1 screening assays to identify the potential of a 

Page 7of13 
chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list 

of chemicals identified for EDSP screening was published on June 14, 2013Pl and includes some 

pesticides scheduled for registration review and chemicals found in water. Neither of these lists 

should be construed as a list of known or likely endocrine disruptors. 

For further information on the status of the EDSP, the policies and procedures, the lists of 

chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our 

website. 

Public Health and Pesticide Epidemiology Data 

Both the OPP Incident Data System (IDS) and the Centers for Disease Control and 

Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event 

Notification System for Occupational Risk-Pesticides (SENSOR) databases were consulted for 

pesticide incident data on the active ingredient (ai) sabadilla alkaloids. The purpose of the 

database search is to identify potential patterns in the frequency and severity of the health effects 

attributed to sabadilla alkaloids exposure. Sabadilla alkaloids is not included in the AHS, and 

therefore this study does not provide information. 

Overall, there are few incidents reported to IDS involving sabadilla alkaloids. For the Main IDS, 

from January 1, 2010 to February 4, 2015, there were no incidents reported involving sabadilla 

alkaloids. In Aggregate IDS, from January 1, 2010 to February 4, 2015, there were 3 incidents 

reported involving sabadilla alkaloids. These incidents were classified as minor severity. 

A review of SENSOR-Pesticides 1998-2011 identifies a total of three cases, stemming from 

three events, involving sabadilla alkaloids (PC Code 00220 I). Two cases involved a single 

active ingredient. Both single ai cases were low in severity. One case was work-related and 

involved a nursery worker who "walked by trees that had been sprayed with a hand sprayer and 

the spray was sti II in the air." This case reported respiratory (cough, respiratory irritation and 

shortness of breath), gastrointestinal (nausea), neurological (headache and muscle weakness) and 

cardiovascular (hypertension) symptoms. The second case involved a homeowner making an 

application to his residence and reported dermal, respiratory (cough) and gastrointestinal 

(diarrhea) symptoms. 

Ill See http://www.regulations.gov/#!documentDetail:D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of 

chemicals. 

Page 8of13 
Based on the low frequency and severity of incident cases reported for sabadilla alkaloids in both 

IDS and SENSOR-Pesticides, there does not appear to be a concern at this time that would 

warrant further investigation. The Agency will continue to monitor the incident information and 

if a concern is triggered, additional analysis will be included in the risk assessment. 

Environmental Justice 

Potential areas of environmental justice concerns, to the extent possible, were considered in the 

human-health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

(http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo 12898.pdt). The OPP 

typically considers the highest potential exposures from the legal use of a pesticide when 

conducting human-health risk assessments, including, but not limited to, people who obtain 

drinking water from sources near agricultural areas, the variability of diets within the U.S., and 

people who might be exposed when harvesting crops. Should these highest exposures indicate 

potential risks of concern, OPP further refines the risk assessments to ensure that the risk 

estimates are based on the best available information. 

Cumulative Risk Assessments 

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to the sabadilla alkaloids and any other substances, and the sabadilla alkaloids do not appear to 

produce a toxic metabolite produced by other substances. For the purposes of this action, 

therefore, EPA has not assumed that the sabadilla alkaloids have a common mechanism of 

toxicity with other substances. For information regarding EPA's efforts to determine which 

chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such 

chemicals, see the policy statements released by EPA' s Office of Pesticide Programs concerning 

common mechanism determinations and procedures for cumulating effects from substances 

found to have a common mechanism on EPA's website at 

http://www.epa.gov/pesticides/ cumulative/. 

Human Studies 

The previous sabadilla alkaloids risk assessments relied in part on data from studies in which 

adult human subjects were intentionally exposed to a pesticide or other chemical. Studies such 

as the Pesticide Handlers Exposure Database (PHED), Outdoor Residential Exposure Task Force 

(ORETF), and Agricultural Handler Exposure Task Force (AHETF) have been reviewed by the 

Agency and found, on the basis of available evidence, to have been neither fundamentally 

unethical nor significantly deficient relative to standards of ethical research conduct prevailing 

when they were conducted. There is no barrier in EPA' s "Protection of Human Subjects" 

Regulation to reliance on these studies. 

Page 9 of 13 
References: 

A uthor Barcode Date T itle 

S.Recore 0427879 6/23/2015 Sabadilla alkaloids: Review of Human Incidents 

US EPA: NIA 9/27/2004 Reregistration Eligibility Decision: Exposure and 

Special Review Risk Assessment on Lower Risk Pesticide 

and Chemicals. 

Reregistration 

Division 

(SRRD) 

Appendix A. Toxicology Data Requirements and Toxicology Profile 

The toxicology requirements (40 CFR 158.340) for the sabadilla alkaloids are presented be low. The 

missing studies are in bold. 

Table A.1. Toxicology Data Requirements. 

Test Technical 

Required Satisfied 

870.1100 Acute Oral Toxicity ...................................................... yes yes 

870.1200 Acute Dermal Toxicity ................................................. yes yes 

870.1300 Acute Inhalation Toxicity ............................................. yes yes 

870.2400 Primary Eye Irritation .................................................. yes yes 

870.2500 Primary Dermal Irritation ............................................. yes yes 

870.2600 Dermal Sensitization .................................................... yes yes 

870.3100 Oral Subchronic (rat) .................................................... yes yes+ 

870.3100 Oral Subchronic (mouse) ........................................... yes no 

870.3150 Oral Subchronic (dog) ............................................... yes no 

870.3200 21 /28-Day Dermal ....................................................... yes no 

870.3250 90-Day Dermal ............................................................. no --- 870.3465 21 /28-Day Inhalation .................................................. nox ---

870.3700a Developmental Toxicity (rat) ....................................... yes yes+ 

870.3700b Developmental Toxicity (rabbit) ............................... yes no 

870.3800 Reproduction (rat) ..................................................... yes no 

870.4200 Carcinogenicity (mouse) ............................................ yes no 

870.4300 Combined Chronic/Carcinogenicity (rat) ................ yes no 

870.5100 Mutagenicity- Gene Mutation - bacterial. ................... yes yes+ 

870.5300 Mutagenicity-Gene Mutation - mammalian .............. yes yes+ 

870.5375 Mutagenicity-Structural Chromosomal Aberrations .. yes yes* 

870.5395 Mutagenicity- Micronucleus ....................................... yes yes+ 

870.6100a Acute Delayed Neurotoxicity (hen) ............................. no ---

870.6100b 90-Day Neurotoxicity (hen) ......................................... no --- 870.6200a Acute Neurotoxicity Screening Battery (rat) ........... yes no 

870.6200b 90 Day Neurotoxicity Screening Battery (rat) ......... yes no 

870.6300 Develop. Neurotoxicity ................................................ no ---

Page 10 of 13 
Table A.1. Toxicology Data Requirements. 

Test Technical 

Required Satisfied 

870.7485 General Metabolism ................................................... yes no 

870.7600 Dermal Penetration ....................................................... no --- 870.7800 lmmunotoxicity .......................................................... yes no 

*fulfilled by guideline 870.5300. + The full study report needs to be submitted to the agency for review to determine the 

acceptability of the study (summary available). x The inhalation toxicity study is typically needed 

if there is the likelihood of signi ficant repeated inhalation exposure to the pesticide as a gas, vapor, or aerosol. 

Table A.2. Toxicity Profile - Sabadilla Alkaloids. 

Acute Toxicitv 

Guideline Study Type MRIDIDoses Results Tox 

Category 

870.1100 Acute Oral - rat 42405901 LDso > 5000 mg/kg JV 

870.1200 Acute Dermal - rabbit 42405901 LDso > 2000 mg/kg lII 

870.1300 Acute Inhalation MRJD not found LCso > 2.10 mg/L IV 

870.2400 Primary Eye Irritation- 42405902 some effects on IV 

rabbit cornea and iris, plus 

redness of conjunctiva 

at I hour, but nonirritating 

(clear) at 24 hours and 

thereafter 

870.2500 Primary Dermal Irritation- 42405902 No irritation IV 

rabbit 

870.2600 Dermal Sensitization- 42405903 Non-Sensitizing (no NIA 

Guinea Pig (Buehler) dermal response in 

screening, induction, 

or challenge ohases) 

Other Toxicity 

Guideline Studv Tvoe MRID/Doses Results 

870.3100 90 day Subchronic Rat MRID: N/A CAL EPA NOAEL=250 mg/kg/day 

summaries LOAEL: 500 mg/kg/day, decreased 

0, 250, 500, and I 000 relative liver weights, elevated serum 

mg/kg/day chemistry (BUN), reduced food 

[Sabadilla Seed - consumption and body weights. 0, 

Technical grade (Veratran 250, 500, and I 000 mg/kg/day 

Technical, purity: 4.83% [Sabadilla Seed - Technical grade 

Total Alkaloids)] (Veratran Technical, purity: 4.83% 

Total Alkaloids)] 

870.3700 Developmental Rat MRJD: NIA CAL EPA Maternal NOAE L: 50 mg/kg/day 

summaries Maternal LOAEL: 250 mg/kg/day 

Dose range: 0, 50, 250, (clinical signs) 

and 500 mg/kg/day 

[Veratran D, Technical, Developmental NOAEL: 250 

assumed 100%] mg/kg/day 

Developmental LOAEL: 500 

mg/kg/day (reduced mean 

fetal weights, as well as misaligned 

and unossified stemebrae) 

Page 11 of13 
Table A.2. Toxicitv Profile - Sa badilla Alkaloids. . Acute Toxicitv 

G uideline Study Type MRID/Doses Results I Tox 

Category 

870.5100 Bacterial Reverse MRID: 462833 11 Negative 

Mutation Assay Dose range: up to 5,000 

μg/ml with or without 

metabolic activation. 

870.5300 In vitro Mammalian Cell MRID: 46283309 Mouse lymphoma cells plated with rat 

Gene Mutation Dose range: up to 1,000 liver metabolic activation were found 

μg/ml with or without to exhibit mutant frequencies 

metabolic activation. approximately two-fold greater than 

the solvent control. No dose-related 

response was observed and significant 

toxicity (growth #50% of the solvent 

control) was observed at the 4 highest 

doses. 

870.5395 Mammalian Erythrocyte MRID: 46283307 Negative 

M icronucleus Dose range: 0, 17.5, 35, 

70 mg/k!!/day 

Table A.3. Summary of Current Toxicological Doses and Endpoints for Sabadilla Alkaloids for Use in 

Dietary, Non-Occupational and Occupational Human Health Risk Assessments. 

RfD,PAD, 

Level of 

Uncertainty/ Concern for 

Exposure/ Point of FQPA Safety Risk 

Scenario Departure Factors Assessment Study and Toxicological E ffects 

Chronic NOAEL = UFA= I Ox Chronic RID NOAEL= 11 mg/kg/day used for risk 

Dietary (All 11 UF11= lOx = cPAD = assessment (estimated by taking 4.83% 

Populations) mg/kg/day FQPA SF= lx 0.11 (total amount of alkaloids in the seed) of 

mg/kg/day the actual dose of230 mg/kg/day) 

Dermal Short- NOAEL = UFA= I Ox Occupational NOAEL: 250 mg/kg/day 

Term ( 1-30 11 UFH= IOx LOC for LOAEL: 500 mg/kg/day, decreased 

days) mg/kg/day FQPA SF= Ix MOE = 100 relative liver weights, elevated serum 

chemistry (BUN), reduced food 

OAF = consumption and body weights. 0, 250, 

100% 500, and I 000 mg/kg/day 

Inhalation NOAEL= UFA= IOx Occupational (Sabadilla Seed - Technical grade 

(Yeratran Technical, purity: 4.83% Total 

Short-Term 11 UF11= lOx LOC for Alkaloids)] ( 1-30 days) mg/kg/day FQPA SF= Ix MOE = JOO 

Cancer (oral, Carcinogenicity studies are not available. 

dennal, 

inhalation) 

Point of Departure (POD)= A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally re levant human 

exposures. NOA EL = no observed adverse effect level. LOA EL = lowest observed adverse effect level. VF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UF11 = potential variation in 

sensitivity among members of the human population (intraspecies). PAD = population adjusted dose (a = acute, c = 

chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. 

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