UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

DATE: Final - May 2 1, 2014 

OFFICE OF CHEMJCAL SAFETY 

D POLUITION PREVENTION 

SUBJECT: Propargite: Human Health Risk Assessment Scoping Document in Support of 

Registration Review 

PC Code: 097601 

MRlD No.: Not Appl.icable 

Petition No.: Not Applicable 

Assessment Type: Scoping 

TXR No.: Not Applicable 

DP Barcode: 0416480 

Registration No.: Not Applicable 

Regu latory Action: Registration Review 

Reregistration Case No.: 0243 

CAS No.: 2312-35-8 

FROM: Marquea D. King, Ph.D., Toxicologist/Risk Asses 

Bonnie Cropp-Kohlligian, Environmental Scientist 

Ivan Nieves, ORE ~ /V"(}) · Risk Assessment Branch IV' . Health Effects Division (7509P) 

THROUGH: E

Risk 

lissa 

Assessment 

Reaves, Ph.D., 

Branch 

Branch 

IV 

Chief f~ 

TO: 

Health Effects Division (7509P) 

Wilhelmena Livingston, Chemical Review Manager 

Risk Management and Implementation Branch IV 

Pesticide Re-Evaluation Division (7508P) 

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

document for propargite to support the registration review process. 

Executive Summary 

HED has considered the available risk assessments for propargite and its toxicity, exposure and 

usage databases, as well as the most current Agency science and assessment policies. HED 

performed this evaluation in order to determine the scope of work necessary to support the 

established tolerances and existing registrations during registration review. The primary source 

of information for this evaluation was the most recent comprehensive Propargite Human Health 
Propargite: Human Health Risk Assessment Scoping Document in Support of Registration Review 

Risk Assessment1 conducted to support the September 2001 USEPA Registration Eligibility 

Decision (RED) for Propargite2. 

Propargite [2-(p-tert-butylphenoxy) cyclohexyl-2-propynyl sulfite] is an organosulfite acaricide used for 

the control of agricultural pests. It is registered for use on a variety of field, fruit, and vegetable crops, 

as well as ornamentals. Tolerances are established inion a number of crop and livestock 

commodities under 40 CFR §180.259 and are expressed in tem1S ofpropargite per se. There are no 

residential uses registered for propargite. Formulations of propargite include emulsifiable 

concentrates (EC) and wettable powders (WP). Depending on the crops, these formulations may be 

applied as broadcast, banded or directed spray or chemigation foliar treatments pre- or postharvest 

using ground or aerial equipment. 

The toxicity, residue chemistry and occupational exposure databases for propargite are adequate 

for registration review and no additional data are required. The toxicity database for propargite 

is considered complete and sufficient for characterization of potential developmental, 

reproductive, carcinogenetic, mutagenic, neurotoxic, and immunotoxic effects. As part of 

registration review, however, the endpoints, doses, and safety factors (SFs) used in the most 

recent human health risk assessment may need to be re-evaluated according to current HED 

policy. Updated exposure and risk assessments may be conducted if there are any significant 

changes to the estimated drinking water concentrations (EDWCs), and/or to the current scenariospecific surrogate handler-exposure data. 

The most prevalent clinical signs associated with this chemical are weight loss and GI (stomach 

and jejunum) perturbations. There was no indication of quantitative or qualitative susceptibility 

in the developmental or reproduction studies. A battery of mutagenicity studies adequately 

demonstrates the lack of mutagenic effects exerted by this chemical. Propargite is classified as a 

B2 Chemical (Probable Human Carcinogen) (TXR No. 001 0461) based upon the presence of rare 

malignant tumors in the jejunum of male and female Crl:CDBR rats. No evidence of 

carcinogenicity was found in the carcinogenicity studies with CD-l mouse or Wistar rats. 

Acute and chronic dietary risk assessments3 were last performed to support the 2001 Propargite 

RED. Previously assessed highly refined acute, chronic non-cancer, and cancer dietary exposure 

and risk analyses were performed on food only. At the 99.9th percentile, 2% of the acute 

Population Adjusted Dose (aPAD) was used for females 13-49 years (the only population 

subgroup identified as relevant for the acute dietary endpoint), and less than 1% of the chronic 

Population Adjusted Dose (cPAD) was used for the general U.S. population and all other 

population subgroups. Cancer dietary risk from food alone was 1.8 x 10 -? for the general U.S. 

population. Risks from potential exposure to propargite in drinking water from all sources were 

evaluated by comparing modeled estimated environmental concentrations (EECs) against 

calculated drinking water levels of comparison (DWLOCs). The modeled acute and chronic 

non-cancer EECs for propargite in drinking water did not exceed the Agency's calculated 

DWLOC values. The modeled cancer EEC for surface water and available surface water 

1 Propargite Revised Human Health Risk Assessment. T. Morton. 9/ 13/200 I. 0276544 

2 http://www.epa.gov/pesticides/reregistrationlpropargite/ 3 Propargite Revised Cancer Dietary Exposure and Risk Analysis for the HED Human Health Risk Assessment. 

T. Morton. 8/28/200 I. 0276547. 

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Propargite: Human Health Risk Assessment Scoping Document in Support of Registration Review 

monitoring data did indicate a concern for cancer from drinking water alone; however, the 

Agency considers these drinking water estimates to be conservative and likely overestimate the 

actual exposure to propargite in fmished drinking water. 

While there are currently no registered residential uses of propargite, residential bystander 

exposures resulting from off-site transport (i.e., spray drift or volatilization) may occur as a result 

of occupational applications of propargite. The need for a bystander risk assessment for 

propargite will be considered during registration review. 

The previous occupational exposure assessment4 covered all exposure scenarios relevant to 

propargite and no occupational handler or post-application risks of concern were identified with 

use of appropriate personal protective equipment (PPE). 

Chemical Use Profile 

Propargite is an organosulfite acaricide used for the control of agricultural pests and its mode of 

action is believed to be inhibition of mitochondrial ATP synthase. It is a non-systemic 

compound causing mortality of mites from interruption of normal metabolism and respiration. 

It is currently registered for food/feed uses on the following: almond, dry beans, com (field, pop 

and sweet), cotton, grape, grapefruit, hops, lemon, nectarine, orange, peanut, 

peppermint/spearmint, potato, sorghum, tea and walnut; however, lemon and tea are not 

currently on end-use products registered in the U.S. Registered commercial use sites for 

propargite include ornamentals and roses not for homeowner use or purchase. Propargite 

formulations include emulsifiable concentrate and as a wettable powder which is applied by 

aerial application, ground boom, chemigation, air blast sprayer, and high pressure hand wand. 

Propargite labels have been amended as required under the propargite RED process with the 

following exception: EPA Registration Number 400-427 still allows application to cherry 

orchards after fruit harvest. This use should be deleted since it is considered a food use 

(ChemSAC 8/25/99) and there is no established tolerance in/on this crop. 

The nomenclature and physiochemical properties of propargite are presented in Tables 1 and 2 of 

Attachment 1. 

Hazard Identificationrr oxicology 

The toxicity database for propargite is complete and sufficient for characterization of potential 

developmental, reproductive, carcinogenetic, mutagenic, neurotoxic, and immunotoxic effects. 

There were no qualitative differences found in the formation of metabolites in mouse versus rat. 

Pharmacokinetic studies revealed that propargite is absorbed through the GI tract 5-7 times faster 

in mice than in rats. Mice also eliminated the material twice as fast as rats. 

4 Propargite: Revised Occupational and Residential Exposure and Risk Assessment for the Reregistration Eligibility 

Decision (RED) Document. S. Tadayon. 7/31/2001. D276513. 

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Propargite: Human Health Risk Assessment Scoping Document in Support of Registration Review 

Propargite is considered corrosive and is irritating in both the eye and dermal rabbit studies, with 

a Tox Category I rating for both. These chemical properties are consistent with incidents of 

workers in the field developing dermal and eye irritation (D419224). Evidence of dermal 

sensitization potential has been noted but due to the irritating properties of the chemical 

conclusive results have not been generated. There is low acute toxicity via the oral and dermal 

routes of exposure. The most prevalent clinical signs is weight loss and target organ for 

propargite is the GI tract (stomach). Adverse effects of overall body weight decreases are 

consistent across time and species. The available studies demonstrate no increased sensitivity to 

rats or rabbits in utero and/or postnatal exposure to propargite. 

The lOx Food Quality Protection Act (FQPA) Safety Factor (SF) for the protection of infants and 

children has been reduced to IX for the following reasons: (1) The toxicology and exposure 

databases are complete and 2) There is no increased qualitative or quantitative susceptibility in 

the rat or rabbit developmental toxicity studies 

Propargite is classified as a B2 chemical (Probable Human Carcinogen) based upon the presence 

of rare malignant tumors of the jejunum in male and female Crl:CDBR rats. There was no 

carcinogenicity seen in CD-I mice nor Wistar rats. An oral slope factor (Q I *) of0.033 x 10"1 

was used for quantification of human cancer risk. Cell proliferation studies were conducted in an 

effort to establish a mode of action for the carcinogenic effects. It was concluded that there was 

insufficient evidence to warrant a re-evaluation of the classification of Propargite or the method 

of quantification of human cancer risk reassessment (MRID 43766801 ). A battery of 

mutagenicity studies demonstrates lack of mutagenic effects upon exposure to propargite. 

Acute and subchronic neurotoxicity studies in rats and an immunotoxicity study, which are 

required in accordance with new data requirements for conventional pesticide registration ( 40 

CFR Part I 58), have not been submitted. However, based on a weight-of-evidence (WOE) 

approach, considering all the available propargite hazard and exposure information, the HED 

Hazard and Science Policy Council (HASPOC) concluded that the acute and subchronic 

neurotoxicity studies and the immunotoxicity study are not needed for propargite at this time5. 

The acute, subchronic, and chronic toxicity profile tables for propargite are included in 

Attachment 2. Toxicity endpoints, points of departure (PODs), and uncertainty/safety factors 

(UF/SFs) were selected for oral, dermal, and inhalation exposure pathways for the Human Health 

Risk Assessment conducted in 2001 (D276544), and these are shown in Attachment 3. 

Upon review of the toxicology data and consideration of all available data including the open 

literature, the endpoints for risk assessment and all uncertainty factors may be re-evaluated 

during registration review to reflect current HED policies. 

Conclusions: The toxicity data base for propargite is considered complete and is adequate for 

assessing potential carcinogenetic, mutagenic, developmental, neurotoxic, immunotoxic, and 

5 Propargite: Summary of Hazard and Science Policy Council (HASPOC) Meeting of April I 0, 2014: 

Recommendations on the Requirement of an Immunotoxicity Study, and the Acute and Subchronic Neurotoxicity 

Studies for Propargite. U. Habiba. 4/10/2014. TXR No. 0056943. 

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Propargite: Human Health Risk Assessment Scoping Document in Support of Registration Review 

reproductive effects. During registration review, the endpoints and safety factors for risk 

assessment may be updated to reflect current policies. 

Residue Chemistry 

The qualitative nature of the residue of propargite in plants and livestock is adequately 

understood. The HED Metabolism Assessment Review Committee (MARC; D256182) 

determined that propargite is the residue of concern for tolerance expression and/or risk 

assessment in plants, livestock, rotational crops and drinking water. Additional data required by 

the HED MARC concerning the fate of the propynyl side chain has been reviewed (D259994) 

and, neither the propynyl fragment nor any metabolites of this side chain are considered a residue 

of concern. Adequate analytical enforcement methods are available. 

Multiresidue method testing data (GLN 860.1360), storage stability data (GLN 860.1380) and 

cotton gin byproducts field trial data (GLN 860.1500) were submitted in response to the 

Propargite Reregistration Eligibility Decision (RED). Additional sweet corn field trial data 

(GLN 860.1 500) were submitted under Section 6(a)(2) notification regarding above tolerance 

residues of propargite in/on sweet corn forage and were considered by ChemSAC (6/3/09). 

These data will be reviewed during registration review. A tolerance for residues ofpropargite 

in/on cotton gin byproducts will need to be established and the currently established tolerance 

in/on sweet corn forage may need to be increased. 

Conclusions: No additional residue chemistry data are required for the propargite registration 

review. Residue chemistry data submitted since the RED will be reviewed and relevant 

tolerances will be reassessed. Additionally. tolerance expressions will be updated to reflect 

current guidance (Knizner, 5/27 /09). 

Dietary Exposure and Risk Assessment 

The most recent dietary exposure and risk assessments (D266001 and D276547) used the Dietary 

Exposure Evaluation Model (DEEMTM) software and consumption data from USDA's 

Continuing Surveys of Food Intakes by Individuals (CSFII), 1989-92. Highly refined acute 

(D266001), chronic non-cancer (D266001) and cancer (D276547) dietary exposure and risk 

analyses were performed on food only using available United States Department of 

Agriculture (USDA) Pesticide Data Program (PDP) monitoring data, magnitude of the residue 

data and percent crop treated data. At the 99 .9th percentile of exposure, 2% of the acute 

Population Adjusted Dose (PAD) was used for females 13-49 years (the only population 

subgroup identified as relevant for the acute dietary endpoint), and less than 2% of the chronic 

PAD was used for the general U.S. population and all other population subgroups. Dietary 

cancer risk for propargite was 1.8 X 1 0"7 based on the QI* for propargite Of 0.033 X 1 o·l 

(mglkg/day)" 1

• 

Risks from potential exposure to propargite residues in drinking water from all sources was 

comprehensively discussed in the 2005 Revised Propargite RED and risks were evaluated by 

comparing estimated environmental concentration (EEC) levels against calculated drinking water 

levels of comparison (DWLOCs). The potential groundwater and surface water exposures to 

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Propargite: Human Health Risk Assessment Scoping Document in Support of Registration Review 

propargite were assessed based on Tier 1 and Tier 2 models, respectively. The acute and chronic 

values were below the acute and chronic DWLOCs and not of concern. However, the cancer 

value exceeded the cancer DWLOC. EPA investigated the available United States Geologic 

Survey (USGS) National Water Quality Assessment (NAWQA) monitoring data for propargite 

to evaluate how it compared to the modeling results. Although the cancer drinking water risk 

estimates from surface water were above the Agency's level of concern, the Agency deemed the 

modeling and monitoring data upon which the estimates were based to be conservative and likely 

overestimate the actual exposure to propargite in drinking water. 

Conclusions: A new dietary exposure and risk assessment may need to be conducted if there are 

changes to the propargite toxicological PODs or UFs or significant changes to the EDWCs. The 

assessment, if conducted, will use the newest version of DEEM and reflect updated consumption 

information. 

Residential Exposure 

The registered uses for propargite are not expected to result in residential exposure; therefore, a 

quantitative residential exposure assessment has not been conducted and would not be required 

for registration review. 

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

occur as a result of applications ofpropargite. The Agency is in the process of evaluating these 

types of exposures and may, as appropriate, develop policies and procedures to identify the need 

for and, subsequently, the way to incorporate these post-application exposures into the Agency's 

risk assessments. 

Conclusions: There are no residential uses currently registered for propargite; therefore, a 

quantitative residential exposure risk assessment is not necessary during registration review. The 

need for spray drift and volatilization risk assessment for propargite will be examined during 

registration review. 

Aggregate Risk Assessment 

In accordance with the Food Quality Protection Act (FQPA), HED must consider and aggregate 

pesticide exposures and risks from three major sources: food, drinking water, and residential 

exposures. The aggregate risk assessment evaluates the combined risk from dietary exposure 

(food and water) and any non-occupational (residential) uses. However, there are currently no 

residential uses for propargite; therefore the propargite aggregate risk assessment includes only 

dietary exposure (food and water). 

Acute 

The 2001 Human Health Risk Assessment acute aggregate risk assessment addressed exposure to 

propargite residues in food and water using the DWLOC approach described above. The 

resulting surface and ground water acute EDWCs of 34 ppb and 0.006 ppb were found to be 

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Propargite: Human Health Risk Assessment Scoping Document in Support of Registration Review 

below the calculated acute DWLOC of2400 ppb for females 13-49 years old, and are therefore 

not of concern. 

Chronic 

Chronic DWLOCs were calculated based on chronic dietary exposures to propargite in food and 

water. Chronic EDWCs of 8.7 ppb and 0.006 ppb for surface and groundwater were likewise 

found to be below the chronic DWLOCs of 1400 ppb for the general U.S. population and 400 

ppb for all infants < 1 year old, and are therefore not of concern. 

Conclusions: In 2001 there were no aggregate (food and water) risk estimates of concern for 

propargite. During registration review, updated aggregate assessments may be conducted as 

required to include any significant change that might occur for toxicological PODs, FQPA and 

uncertainty factors, dietary exposure estimates, or EDWCs. Emerging policies related to 

pesticide drift and volatilization assessments may dictate further changes to the existing 

aggregate risk assessment. 

Occupational Exposure 

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

agricultural uses of propargite. Propargite is currently formulated as an emulsifiable concentrate 

liquid and a wettable powder. The application rates range from 0.5 to 4.8 lbs propargite/acre. It 

can be applied 2 to 3 times per year to agricultural crops from early season up to harvest 

time. Equipment used include aerial, chernigation, groundboom, airblast, and high pressure 

handwand. The most current occupational and residential memo is a revised assessment for the 

re-registration eligibility decision (RED) document in 2001 (D276513; 7/31/01; S. Tadayon). 

The Reregistration Eligibility Decision (RED) document for propargite was signed on September 

2001 . Subsequent to the Agency's review of public comments, the propargite RED was revised 

in December 2005. In September 2007, the propargite RED was amended to lower airblast 

maximum spray application rate (from 4.5 ai/ A to 4.05 ai/ A), and require enclosed cab 

applicators to wear additional personal protective equipment (PPE) (long-sleeved shirt, long 

pants, coveralls, shoes and socks) plus chemical resistant head gear. 

Occupational Handlers 

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

currently registered use pattern ofpropargite. Chemical-specific data was submitted by the 

registrant to assess potential exposure to pesticide handlers. These data included the following 

studies: 

• Airblast applicator exposure studies (MRID Nos. 418486-05 and 420997-02) 

• Groundboom applicator exposure study (MRID No. 418486-05) 

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Propargite: Human Health Risk Assessment Scoping Document in Support of Registration Review 

Occupational handler exposure based on surrogate unit exposures from the Pesticide Handlers 

Exposure Database (PHED) was used when no chemical specific data were available. Previous 

risk calculations were based on the maximum application rates and assumed maximum area 

treated per day. Handler exposure and risk were calculated at baseline (long pants, a longsleeved shirt, no chemical-resistant gloves, and no respirator) and with personal protective 

equipment (PPE) when necessary (e.g., chemical-resistant gloves, respirators, and engineering 

controls). 

Short-and intermediate-term exposure durations resulted in margin of exposures (MOEs) from 

less than 1 to 2,600. However, MOEs were greater than the level of concern (LOC = 1 00) at the 

maximum level of protection as thus not of concern (e.g., various levels of PPE or engineering 

controls). Cancer potential risk estimates resulted in values ranging from 3.2 x 10·

3 to 2.7 x 10·6 

at baseline, 2.8 x 104 to 5.3 x 10·7 at various level of PPE and 6.1 x 10·5 to 6.9 x 1 o-s with 

engineering controls. 

Occupational Post-Application 

There are potentially significant short and intermediate-term post-application exposures to 

workers entering treated fields for post-treatment activities, e.g., weeding, pruning, irrigating, 

harvesting. For the 2001 RED, post application exposure studies were conducted by the 

registrant and submitted to the Agency. These studies were acceptable and included passive 

dosimetry data, along with dislodgeable foliar residues (DFRs). 

Duration of exposure activities (i.e., days engaged in sorting/packing, irrigation, harvesting, etc.) 

were presumed to be of short (1 to 7 days) and intermediate (7 to 90 days)-tenn durations. Reentry intervals (REis) for the potential dermal contact ranged from 0 to 42 days. 

For cancer, a screening estimate was developed because lifetime use data were not available. 

Based on screening level assumptions, the cancer probabilities on the day the REis were 

estimated used the subchronic endpoints and ranged from 9.74xl0-6 to 1.00xl 04 . 

Conclusions: The occupational exposure database is adequate to support the registration review 

process for propargite. Previous occupational handler and post-application exposure assessments 

did identify risks of concern based on chemical-specific data. Registration review may include 

updated handler and post application risk estimates based on current policies. During 

registration review, the validity and applicability of these data will be considered pending 

analysis. 

Public Health and Pesticide Epidemiology Data 

For this evaluation, 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 propargite (PC codes: 09760 l ). The 

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

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Propargite: Human Health Risk Assessment Scoping Document in Support of Registration Review 

the health effects attributed to propargite exposure. Propargite is not included in the AHS, and 

therefore this study does not provide information for this report. 

Conclusions: The Agency has reviewed the available incident data and concludes that based on 

the low frequency and severity of incident cases reported for propargite 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 (0419224). 

Tolerance Assessment and International Harmonization 

U.S. permanent tolerances are established under 40 CFR § 180.259 for the registered uses of 

propargite inion a number of commodities. Codex and Canadian maximum residue limits 

(MRLs) for residues ofpropargite have been established for some of the same commodities 

which have tolerances in the United States (U.S.). Mexico adopts U.S. tolerances and/or Codex 

MRLs for its export purposes. While residue definitions are compatible, a number of U.S. 

tolerances are not numerically compatible with Codex or Canadian MRLs. The tolerance residue 

levels may need to be examined during registration review to determine if further harmonization 

can be achieved. See Appendix 4. 

Environmental J ustice 

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

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.epa.gov/compliance/resources/policies/ej/exec order 12898.pdf The Office of 

Pesticide Programs (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 may be exposed when harvesting crops. Should these high 

exposures indicate potential risks of concern, OPP will further refine the risk assessments to 

ensure that the risk estimates are based on the best available information. 

Cumulative Risk Assessment 

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 propargite and any other substances and propargite does not appear to produce a toxic 

metabolite produced by other substances. For the purposes ofthis tolerance action, therefore, 

EPA has not assumed that propargite has 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/. 

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Propargite: Human Health Risk Assessment Scoping Document in Support of Registration Review 

Human Studies 

The 2001 RED and 2001 risk assessment relied in part on data from studies in which adult 

human subjects were intentionally exposed to a pesticide or other chemical. These data, which 

include studies from Pesticide Handler Exposure Database (PHED) 1.1; the Agricultural Handler 

Exposure Task Force (AHETF) database; the Agricultural Reentry Exposure Task Force (ARTF) 

database; and Exposure Science Advisory Committee (ExpoSAC) Policy 14 (Standard Operating 

Procedures for Seed Treatment), are ( 1) subject to ethics review pursuant to 40 CFR 26, (2) have 

received that review, and (3) are compliant with applicable ethics requirements. For certain 

studies, the ethics review may have included review by the Human Studies Review Board. 

Descriptions of data sources, as well as guidance on their use, can be found at the Agency 

website6. 

Endocrine Disruption 

As required by Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and Federal Food, 

Drug, and Cosmetic Act (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 propargite, 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), propargite is 

subject to the endocrine screening part of the Endocrine Disrupter 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 11 screening assays to identify the potential of a 

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, ofthe 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 

6 http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html 

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Propargite: Human Health Risk Assessment Scoping Document in Support of Registration Review 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of67 

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, 20137 and includes some 

pesticides scheduled for registration review and chemicals found in water. 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. 8 

Propargite is on List 1 for which EPA has received all the required Tier I assay data. The 

Agency is currently reviewing all the assay data received for the appropriate List 1 chemicals 

and planning to make the conclusions of those reviews available in early 2015. 

Risk Assessment Updates and Data Deficiencies 

• 

• There are no data deficiencies for propargite. 

• Updated exposure and risk assessments may be conducted if there are any significant 

changes to propargite toxicological endpoints, points of departure, Food Quality 

Protection Act safety factor or other uncertainty factors, standard operating procedures, 

or exposure data or assumptions. 

• Residue chemistry data submitted since the RED will be reviewed and relevant tolerances 

will be reassessed. Additionally, tolerance expressions will be updated to reflect current 

guidance (Knizner, 5/27 /09). 

• EPA Registration Number 400-427 allows application to cherry orchards (a food use) 

after fruit harvest. This use should be deleted since there is no established tolerance inion 

this crop (ChemSAC 8/25/99). 

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

chemicals. 

8 http://www.epa.gov/endo/ 

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Propargite: Human Health Risk Assessment Scoping Document in Support of Registration Review 

References 

Table 1. Memoranda Relevant to Registration Review•. 

Author Barcode Date Title 

E. Evans and S. 0419224 4/09/2014 Propargite: Tier 1 Review of Human Incidents Recore 

Dodd,N. D256182 06/07/99 Propargite. HED Metabolism Assessment Review 

Committee Meeting on 5/ 18/99. Residues of Concern 

in Plants, Animals, and Water. 

Dodd, N. D256206 06/07/99 Propargite. Plant and Animal Metabolism Data 

Requested by the Metabolism Assessment Review 

Committee on 5/ 18/99. 

Shalla!, S. D259994 !l/02/99 Information on the fate of the sulfide side chain of 

Propargite (MRID 44920901 ). 

Stokes, J. D250257 01/20/00 Residue Chemistry Chapter For The Propargite 

Reregistration Eligibility Decision (RED) Document. 

Morton, T. D266001 05/24/00 Revised Anticipated Residues and Acute, Chronic, and 

Cancer Dietary Exposure and Risk Analyses for the 

HED Human Health Risk Assessment. 

Morton, T. D276547 08/28/01 Revised Cancer Dietary Exposure and Risk Analysis for 

the HED Human Health Risk Assessment. 

S. Tadayon D27651 3 7/31 /0l Propargite: Occupational and Residential Exposure and 

Risk Assessment for the Reregistration Eligibility 

Decision (RED) Document. 

Morton, T. D276544 09/ 13/01 HED's Revised Human Health Risk Assessment for 

Propargite. 

Lin, J. 0350518 06/18/08 Review of the Small-Scale Drinking Water Monitoring 

Andrews, N. Study for Propargite. (MR1D 473141 01) 

Knizner, S. None 05/27/09 Interim Guidance on Tolerance Expressions 

Morton, T. 0373907 3/31 /11 Propargite: Storage Stability Data for Com Processed 

Commodities, Peanut Processed Commodities, and 

Almond Raw Agricultural Commodities. 

I. This table only includes references to final versions. Previous versions of these documents are available, but have been superseded. 

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Propargite: Human Health Risk Assessment Scoping Document in Support of Registration Review 

Attachments: 

Attachment 1: Chemical Identity and Physicochemical Properties 

Attachment 2: Propargite Acute, Subchronic, and Chronic Toxicity Profile 

Attachment 3: Propargite Toxicological Doses and Endpoints 

Attachment 4: Propargite International Residue Limits 

Attachment 1. Chemical Identity and Physicochemical Properties 

Table 1. Test Compound Nomenclature. 

Compound Chemical Structure 

"·'~ // 0 

(;' 's 

II ,o~~ 0 

Common name Propargite 

Company experimental name NA 

IUPAC name 2-( 4-tert-butylphenoxy)cyclohexyl prop-2-ynyl sulfite 

CAS name 2-[4-(1, 1-dimethylethyl) phenoxy] cyclohexyl 2-propynyl sulfite 

CAS# 2312-35-8 

Table 2. Physicochemical Properties of Propargite. 

Parameter Value Reference 

Boiling point/range Decomposes before boiling 40171201 & 42585202 

pH 6.3 (1% dispersion in distilled water) 40171201 & 42861203 

Density 1.12 g/m122°C 473916-03 

Water solubility ( 25°C) 1.9ppm 40358403, 42319303, & 

42319304 

Solvent solubility (mg/L) >200 giL in acetone, dichloromethane, 40358403, 42319303, & 

hexane, methanol, and toluene 42319304 

Vapor pressure at 25°C 4.49 x J0·

9 mm Hg 41003603 & 45920501 

Dissociation constant (pK.) pKa > 12. No deprotonation (i.e., ionization) 423 19302 

was observed in water solutions 

Octano1/water partition coefficient Log(Kow) 5.8 @ 25 c 40171201 , 42319302& 

42861202 

UV /visible absorption spectrum E = 1387 (log E = 3.14) at 276 nm 45905506 

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Propargite: Human Health Risk Assessment Scoping Document in Support of Registration Review 

Attachment 2. Propargite Acute, Subchronic, and Chronic Toxicity Profile 

Acute Toxicity- Propargite -- --- -- - ! 

Guideline Study Type MRID(s) Results Toxicity 

No. Category 

!-----

870.1100 Acute Oral 42857001 LD50 = 2639 mglkg for males III 

2947 mglkg for 

females 

2800 mglkg 

combined 

870.1200 Acute Dermal 42857002 LD50 > 2000 mglkg lii 

f-- -

870.1300 Acute inhalation 42857003 LC50 = 0.95 mg/L for males lii 

0.95 mg/L for 

females 

0.89 mg/L combined 

870.2400 Primary Eye Irritation 42857004 Corrosive I 

870.2500 Primary Skin Irritation 42857005 Corrosive I 

870.2600 Dermal Sensitization 42857006 Sensitizer N/A 

Subchronic, Chronic, and Other Toxicity Profile- Propargite 

Guideline No./ MRID No. (year)/ Results Study Type Classification /Doses 

870.3700a MRID 41346501 (1990) No treatment-related changes were seen in gravid uterine acceptable/guideline Prenatal developmental 0, 6, 12, 18,25, 105 weight, post implantation loss, fetal viability, sex ratio, or in rats mglkglday soft tissue variations/malformations 

870.3700b MRJD41336301 ( 1989) No treatment-related changes were seen in post 

Prenatal developmental acceptable/guideline implantation loss, fetal viability, sex ratio, or soft tissue 

in rabbits 0, 2, 4, 6, 8, I 0 mglkglday variations/malformations 

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Propargite: Human Health Risk Assessment Scoping Document in Support of Registration Review 

No treatment-related effects were seen in male fertility 

index, female fertility index, or gestation index.. Pup 

viability, sex ratio, gross or histopathological changes in the 

testes, epididymides, seminal vesicle, coagulating gland, 

prostate, ovaries, uterus, cervix, vagina, or pituitary. 

870.3800 MRID 41352401 (1990) 

Reproduction and acceptable/guideline NOTE: Table 3 on Page 5 of the OSRI presents incidence 

fertility effe.cts 0, 4, 20, or 40 mglkg/day data for microscopic observations in this study. 

Observations in the uterus indicate "not remarkable" for 

7/24 controls and 6/25 high dose animals. 

The DER, however, states that "there were no compoundrelated increases in gross necropsy or microscopic 

abnormalities." 

No treatment-related changes were seen in testes weights. 

The absolute mean ovarian weight was decreased (54%) in 

females only at the high dose ( 44 rn/k/d) and the absolute 

kidney weights were decreased in males (35%) and females 

(34%) at the high dose. The increase in relative weights of 

870.4100 b MRID41751401 (1991) adrenals, liver, kidneys, thyroid, and ovaries at the high 

Chronic toxicity in acceptable/guideline dose were attributed to the severe body weight loss in both 

0, 5, 38 or 44 mglkg/day males (23.3%) and females (25%) at the high dose. The dogs (beagle) for l year initial high dose of2500 ppm was reduced to 1875 ppm (44 

rn/k/d) after first 9 weeks due to severe weight loss (29%), 

decreased food consumption and reduced heart and kidney 

weights. No treatment-related histopathological lesions 

were seen in the, testes, epididymides, prostate, mammary 

glands, ovaries, uterus, pituitary, adrenal, or thyroid glands. 

No treatment-related changes were seen on the testes and 

epididymides. At the interim sacrifice (week 52), relative 

liver and kidney weights were increased in both sexes when 

MRID 41750901 (1991) compared to controls but at termination the relative weights 

of these organs were comparable to controls. Ovarian and 

870.4300 acceptable/guideline 

uterus weights were not obtained. 

Chronic Toxicity/ M: 0, 2 .38, 3.83, 19.24, No treatment-related histopathological lesions were seen in 

Carcinogenicity in rats 38.87 mglkg/day the testes, epididymides, seminal vesicle, prostate, penis, F: 0, 2.95, 4.68, 23.58, preputial gland, mammary glands, ovaries, cervix, vagina, 49.36 mg/kg/day clitoral glands, pituitary, adrenal or thyroid glands. 

Endometrial polyps of the uterus were seen in 2%, 0%, 

12%, 15%, and 3% at the control, low, mid, mid-high and 

high dose groups, respectively. 

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Propargite: Human Health Risk Assessment Scoping Document in Support of Registration Review 

Attachment 3. Toxicological Doses and Endpoints 

EXPOSURE DOSE ENDPOINT STUDY TYPE/ 

SCENARIO (mg/kg/day) MRID 

Acute Dietary- NOAEL=8 Increased incidence of fused sternebrae in fetuses at Developmental Toxicity 

females 13-50 UF = 100 I 0 mg/kglday (LOAEL). in Rabbits 

FQPA= I 41336301 

Acute Dietary- NOAEL= N/A No relevant single exposure endpoint was identifi ed. 

gene ral population ur = N/A N/A 

FQPA = I 

Acute RID (females 13-50) == 0.08 mg/kg/day Acute RID (Gen. Pop.) = N/A 

aPAD = 0.08 mglkglday 

Chronic Dietary NOAEL = 4 Decreased body weight/ body weight gain and Chronic Feeding and 

UF = 100 increased mortality at 19 mglkglday (LOAEL) for Ca rcinogenicity in Rats 

FQPA= I males. 41 750901 

Chronic RID = 0.04 mglkg/day 

cPAD = 0.04 mglkglday 

Cancer Risk -1 ·I Q 1 

• = 0.33 X tO (mglkglday) 

Short-Term I NOAEL=6 Decreased maternal body weight gain at 8 mg/kg/day Developmental Toxicity 

(Dermal) MOE = 100 (LOAEL). in Rabbits 

4 1336301 

Intermediate-Term I NOAEL= 4 Reduction in body weight gain and food consumption Reproductive Toxicity 

(Dermal) MOE = 100 at 20 mg/kglday (parental LOAEL). in Rats 

41 35240 1 

Long-Term I NOAEL= 4 Decreased body weight I body weight gain and Chronic Feeding and 

(Dermal) MOE = 100 increased mortali ty at 20 mg/kg/day (LOAEL). Carcinogenicity in Rats 

4 1750901 

Short Term 2 

LOAEL= Acute Inhalation in 

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Propargite: Human Health Risk Assessment Scoping Document in Support of Registration Review 

l Intermediate Term 0.31 mg/L or 50 

mg/kg Increased mortality at 0.3 I mg/L (LOAEL) in males. 

MOE = 1000 

Long Term l 

I 

A 14% dermal absorption f.tctor will be used for risk assessment and an MOE of 100. z 

An MOE of 1000 was selected for inhalation, including a lOX factor due to lack of a NOAEL, severity of 

effects at the lowest dose tested, and 4 hour duration. 

3 [conversion mg/L to mg/kg: 0.31 mg/L X 10 Uhr X 4 hrs = 12.4 mg; 12.4 mg /0.25 kg= 49.6 mg/kg] 

Attachment 4. International Residue Limits 

Propargite ( 097 60 1 ; 12/11113) 

Summary ofUS and International Tolerances and Maximum Residue Limits 

Residue Definition: 

us Canada Mexico2 Codex3 

40 CFR § 180.259: 2-(4-tert- Propargite 

Plants/Livestock: Propargite (2-(p- butylphenoxy)cycloh The residue is fat soluble. 

exyl prop-2-ynyl tert-butylphenoxy) cyclohexyl 2- sulphite propynyl sulfite) 

Commodity1 

Tolerance (ppm) !Maximum Residue Limit (mglkg) 

Canada Mexico2 us Codex 

Almond 0.1 0.1 (*) 

Almond, hulls 55.0 50 

Bean, dry, seed 0.2 5 beans 0.3 beans; broad bean; 

chickpea; lipin (all dry) 

Cattle, fat 0.1 

Cattle, meat 0.1 0.1 (*)(fat) meat (from 

mammals other than marine 

mammals 

Cattle, meat byproducts 0.1 0.1 (*)edible offal 

(mammalian) 

Citrus, oil 30.0 

Com, fie ld, forage 10.0 

Com, field, grain 0.1 0.1 (*)maize 

Com, field, stover 10.0 

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Rats 

42857003 
Propargite: Human Health Risk Assessment Scoping Document in Support of Registration Review 

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition: 

us I Canada Mexico2 Codex3 

Com, pop, grain 0.1 

Com, pop, stover 10.0 

Com, sweet, forage 10.0 

Corn, sweet, stover 10.0 

Cotton, undelinted seed 0.1 I . I . cotton seed 

1.2. cotton seed oil, edible 

Egg 0.1 0.1 (*) 

Goat, fat 0.1 

Goat, meat 0. 1 0.1 (*)(fat) meat (from 

mammals other than marine 

mammals 

Goat, meat byproducts 0.1 0.1 (*)edible offal 

(mammalian) 

Grain, aspirated fractions 0.4 

Grape 10.0 7 7 

Grapefruit 5.0 5 citrus fruits 3 citrus fruits 

Hog, fat 0.1 

Hog, meat 0. 1 0.1 (*)(fat) meat (from 

mammals other than marine 

mammals 

Hog, meat byproducts 0.1 0.1 (*)edible offal 

(mammalian) 

Hop, dried cones 100.0 30 hops (dried) 100 hops dry 

Horse, fat 0.1 

Horse, meat 0.1 0.1 (*) (fat) meat (from 

mammals other than marine 

mammals 

Horse, meat byproducts 0.1 0.1 (*) edible offal 

(mammalian) 

Lemon 5.0 5 citrus fruits 3 citrus fruits 

Milk, fat (0.08 ppm in milk) 2.0 0.1 (*)milks F 

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Propargite: Human Health Risk Assessment Scoping Document in Support of Registration Review 

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition: 

us I Canada Mexico2 Codex3 

Nectarine 4.0 7 4 stone fruits 

Orange 10.0 5 citrus fruits 3 citrus fruits 

Peanut 0.1 0.1 (*) 

Peppermint, tops 50.0 

Poultry, fat 0. 1 

Potato 0.1 0.03 

Sheep, fat 0.1 

Sheep, meat 0.1 0.1 (*)(fat) meat (from 

mammals other than marine 

mammals 

Sheep, meat byproducts 0.1 0.1 (*) edible offal 

(mammalian) 

Sorghum, grain, forage 10.0 

Sorghum, grain, grain 5.0 

Sorghum, grain, stover 10.0 

Spearmint, tops 50.0 

Tea, dried 10.0 5 tea, green, black (black 

fermented and dried) 

Walnut 0.1 0.3 

MRLs With No US Equivalent 

Apples 3 3 

Apple juice 0.2 

Citrus pulp, dry 10 

Dried grapes (=currants, 12 

raisins and sultanas) 

Grape juice 1 

Grape pomace, dry 40 

Maize flour 0.2 

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Propargite: Human Health Risk Assessment Scoping Document in Support of Registration Review 

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition: 

us I Canada Mexico2 Codex3 

Maize oil, crude 0.7 

Maize oil, edible 0.5 

Orange juice 0.3 

Peaches 7 

Peanut oil, crude 0.3 

Peanut oil, edible 0.3 

Plums 5 

Poultry, meat 0. I (*)(fat) 

Poultry, edible offal of 0.1 (*) 

Tomato 2 

Completed: M. Negussie/ 12/ 12/2013 

1 Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and 

not those proposed by the applicant. 

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes. 

3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = 

processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the 

fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC. 

(c) Tolerances with regional registrations. Tolerances with regional registration, as defined in § 180.1 (1), are 

established for residues of propargite in or on the following raw agricultural commodities: 

Commodity Parts per million 

Com, sweet, kernel plus cob with husks removed 0.1 

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