UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

DATE: 12/05/2013 

OFFICF- OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

SUBJECT: Dithiopyr. Human Health Assessment Scoping Document in Support of Registration Review 

PC Code: 128994 

MRID No.: Not Applicable 

Petition No.: Not Applicable 

Assessment Type: Single Chemical 

Aggregate 

TXR No.: Not Applicable 

FROM: 

DP Barcode: 041 3659 

Registration No.: Not Applicable 

Regulatory Action: Registration Review Scoping 

Reregistration Case No.: Not Applicable 

CAS No.: 97886-45-8 

THROUGH: Ana Rivera-Lupiariez, Chemist JtJJ/. /'""'\ ' -~~­ Michael Metzger, Branch Chief -~ ~ 

Risk Assessment Branches V & VII 

TO: 

Health Effects Division (7509P) 

Veronica Dutch, Chemical Review Manager 

Risk Management and Implementation Branch V 

Pesticide Re-evaluation Division (7508P) 

Executive Summary 

The HED Dithiopyr Registration Review Team has evaluated the scientific database for the 

pesticide dithiopyr to determine the scope of work necessary to support the existing registration. 

Dithiopyr (S,S'-dimethyl 2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-

pyridinedicarbothioate ), a substituted pyridine herbicide, is registered by EPA for use to control 

crabgrass and broad leaf weeds in turf and ornamentals. Currently, there-are no agricultural food 

Page 1 of 10 
uses for dithiopyr. Although a tolerance petition to support the import of treated brown rice was 

considered in 1992, no tolerances were established. Disciplinary and peer review documents in 

the EPA databases were the primary resources for this document. 

Drinking water, occupational, and residential exposures to dithiopyr are possible; therefore, a 

quantitative human health risk assessment is required under registration review for the existing 

uses of dithiopyr. 

HED notes that dithiopyr has not been through a comprehensive endpoint selection process 

(chronic RID and carcinogenicity assessments have been completed); a Toxicology Science 

Advisory Council (ToxSAC) meeting is needed during registration review to determine toxicity 

endpoints for this chemical. The HED Hazard and Science Policy Council (HASPOC) met on 

l l/7/13 and determined that an inhalation study is required; however, the requirements for acute 

and subchronic neurotoxicity and immunotoxicity studies were waived. At this time, no 

aggregate, dietary, occupational or residential risks of concern have been identified for this 

chemical. 

Introduction 

The HED Dithiopyr Registration Review Team has evaluated the potential for human exposure 

from use of this herbicide. The purpose ofthis screen is to determine whether sufficient data are 

available and whether a human health risk assessment is required to support registration review. 

In preparation of this memo, HED considered all relevant dithiopyr reports in the EPA databases. 

A full list is presented in the reference section of this document. 

Dithiopyr is used as a pesticide to control crabgrass and broadleaf weeds in turf and ornamental 

plants. Dithiopyr is formulated as an emulsifiable concentrate, water soluble packets, and as a 

granular product; it can be applied by ground-based and handheld equipment to residential 

turf/ornamentals, industrial areas, commercial turf, and golf courses. Short-term and 

intermediate-term occupational exposures are expected based on the registered use pattern. 

Short-term residential exposures are expected based on the registered use pattern. 

Hazard Identification/Toxicology 

The toxicity database for dithiopyr is complete except for an inhalation study. HASPOC has 

determined that the inhalation study is required (TXR 0056812, J. Leshin, 11119/20 13). The 

HASPOC also recommended waiving the requirements for the ACN/SCN and immunotoxicity 

studies. The toxicity DERs will be re-assessed for establishing LOAEL and NOAEL values 

based on current toxicity policies, and then reviewed by the ToxSAC. 

There are no recent comprehensive human-health risk assessments available for dithiopyr. Other 

than the oral RID, endpoints for other exposure scenarios (i.e., inhalation, dermal, incidental 

oral) have not been identified in these previous assessments. Dithiopyr underwent an RID 

Committee review meeting in 1997, and a CARC review in 1993. The RID Committee 

recommended that a chronic RID be established based on a combined chronic 

toxicity/carcinogenicity study in the rat. A NOAEL of 0.36 mg/kg/day was identified from the 

Page 2 of 10 
rat study based on liver and kidney toxicity observed at 3.63 mg/kg/day. An uncertainty factor 

of 100 was applied to the NOAEL to account for inter- and intra-species variation, resulting in a 

chronic RID of 0.0036 mg/kg/day. Dithiopyr was classified as GroupE- no evidence for 

carcinogenicity in humans. As a basis for the carcinogenicity decision, the CARC indicated that 

there was no increase in malignancy, a lack of genotoxicity, and that dithiopyr does not have any 

structural similarity to known chemical carcinogens. 

On the basis of a preliminary review of the toxicity database for dithiopyr, the following 

tentative conclusions regarding the toxicity of this chemical can be drawn. Technical grade 

dithiopyr has low acute toxicity via oral, dermal and inhalation routes of exposure. Technical 

dithiopyr is not a dermal sensitizer. A primary eye irritation study in rabbits indicated no corneal 

opacity but there was irritation that was reversible. Mild or slight irritation was noted in a 

primary skin irritation study in the rabbit. The subchronic and chronic oral toxicity studies in 

revealed liver and kidney toxicity in rats, mice and dogs. 

A LOAEL of 1000 mglkg/day, based on increased absolute and relative (to body weight) liver 

weights was identified in a 21-day dermal toxicity study in the rat. The NOAEL was 500 

mg/kg/day. Limited to transient mild irritation was noted in some animals in all dose groups. 

Developmental toxicity studies in rabbits and rats identified developmental NOAELs = 1,000 

mg/kg/day, the highest dose tested. No treatment-related adverse effects on reproductive 

parameters (i.e., mating, fertility, gestation indices, and length of gestation) were observed in the 

2-generation reproductive toxicity study in the rat. In addition, there were no indications of 

treatment-related effects on mean number of pups/litter, sex ratio or pup viability in both 

generations. The results of mutagenicity studies (Ames assay, CHO/HGPRT mutation assay, 

and an unscheduled DNA synthesis in rat hepatocyte culture) indicated that dithiopyr was not 

mutagenic under test conditions. 

Conclusions: The toxicity database for dithiopyr is complete except for a subchronic inhalation 

toxicity study. A ToxSAC meeting will be scheduled for endpoint selection during registration 

review. 

Residue Chemistry 

Dithiopyr is not currently registered as a pesticide for use in any food commodities; therefore, 

evaluation of residues in crops is not needed. A search of the dithiopyr residue chemistry 

database indicates that a petition to establish a tolerance on imported brown rice was submitted 

in 1992. Although no tolerance was established, the residue of concern in rice was determined to 

be parent dithiopyr and its dicarboxylic acid metabolite, for both enforcement and risk 

assessment purposes. Deficiencies identified included an insufficient number of field trials and 

inadequate storage stability data (D169452, J. Stokes, 30-JUL-1992). These deficiencies will be 

of concern only if new dithiopyr uses on agricultural crops are proposed. 

Conclusions: The residue chemistry database supports the registered uses of dithiopyr. 

Page 3 of 10 
Dietary Exposure 

The established pesticide uses on turf and ornamentals may result in dietary exposure through 

drinking water consumption. No food-based exposure is anticipated as there are no registered 

food uses in agricultural commodities. A dietary exposure assessment for dithiopyr will be 

conducted in registration review, once estimated drinking water concentrations (EDWCs) are 

determined by the Environmental Fate and Effects Division (EFED). 

Conclusions: A dietary exposure assessment to include drinking water exposure will be 

conducted registration review. 

Residential Exposure 

Based on a review of past dithiopyr document reviews and risk assessments, no quantitative or 

qualitative non-occupational exposure assessment has been conducted to date. Therefore, a 

quantitative residential exposure assessment to address residential handler, post-application, and 

bystander exposure is needed during registration review. 

Residential Handlers 

Based on the current use pattern, there is potential for residential handler exposure. Dithiopyr is 

mainly applied to residential and industrial turf (e.g., golf courses and other non-residential turf 

areas such as industrial parks, sod farms, seed farms, and professionally managed sports fields), 

although it is registered for use on nonbearing fruit and nut trees. It is not restricted from 

purchase or use by residential handlers. Therefore, during registration review HED anticipates 

conducting a residential handler assessment to address dermal and inhalation exposure using the 

most recent exposure methodology and toxicological endpoints/points of departure. 

Residential Post-Application 

Based on the current use pattern, there is potential for post-application exposure (dermal, 

incidental oral) to individuals coming into contact with treated residential turf, for recreational 

golfers, and individuals contacting treated turf in commercially treated areas. Since dithiopyr is 

formulated as a granular product, HED also intends to address incidental ingestion of granules as 

part of the residential post-application assessment. 

In accordance with the updated Part 158 data requirements (2007), a turf-transferrable residue 

(TTR) study is required for all occupational (e.g., sod farms) or residential turf uses; TTR data 

are not available for dithiopyr. As part of the recent revision to the Health Effects Division's 

2012 Standard Operating Procedures for Residential Pesticide Exposure Assessment, HED 

analyzed all of the available TTR data and selected new liquid and granular default values for the 

fraction of the application rate available for transfer after a turf application (FAR)· This default is 

0.2% for granular formulations. Of the available TTR studies submitted to the Agency, the 

maximum FAR value seen using a granular product was 0.69% or 3.5 times higher than the 

default residue transfer value. Therefore, HED has decided that a calculated MOE of 

approximately 10 times higher than the LOC (e.g., an MOE >1,000 if the LOC = 100) using the 

default residue transfer values would provide an adequate margin of safety for any potentially 

Page 4 of 10 
higher residues seen in a chemical-specific TTR study (HED Memo, 12/12/12, "Guidance/or 

Requiring/Waiving TurfTransferrable Residue (ITR) and Disiodgeabfe Foliar Residue (DFR) 

Studies"). While a chemical-specific TTR study is available, substantive data quality issues were 

identified during Agency review. Because of the issues identified, HED completed screening 

level risk estimates based on default TTR values. For the current uses of dithiopyr, a TTR study 

will not be required for Registration Review since estimated dermal (and incidental oral) MOEs 

for all residential post-application scenarios are greater than 1000. Ifthe use pattern and/or 

toxicological points of departure change in the future, this requirement may be revisited. 

Residential Bystander Exposw-es 

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

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

types of exposures and as appropriate, plans to 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. The need for spray drift and volatilization risk assessment for 

dithiopyr will be examined during registration review, although HED anticipates a qualitative 

residential bystander exposure assessment based on the high turf application rate relative to the 

agricultural application rate. 

Conclusions: HED anticipates conducting a new risk assessment to address the short-term 

handler and post-application dermal exposure potential for recreational golfers and individuals 

(adults and children) contacting residential and commercially treated turf. Additionally, HED 

intends to assess incidental oral exposure potential based on turf contact and the incidental 

ingestion of dithiopyr formulated as granules. TTR data are not required for dithiopyr based on a 

preliminary screen of estimated risks from contacting treated turf, and based on tentative 

endpoint selection and 2012 Residential SOPs. The potential for residential exposures resulting 

from off-site transport (e.g., spray drift or volatilization) may need to be quantitatively evaluated 

for dithiopyr during the registration review process. 

Combined Drinking Water Plus Residential Exposure Risk Assessment 

Combined drinking water plus residential exposure to dithiopyr will be examined as part of 

registration review. These routes of exposure are anticipated given the use pattern (i.e., turf and 

ornamentals) of the chemical and, therefore, the risk from both sources will be assessed as part of 

the registration review of dithiopyr. 

Occupational Exposure 

Dithiopyr is not currently registered for use on agricultural crops, although it is registered for use 

on commercial turf, golf courses, and other professionally managed turf areas. There is potential 

for short- and intermediate-term occupational exposure to dithiopyr during handling (mixing, 

loading, and applying) and post-application activities. The LOC for dermal and inhalation risk 

estimates is an MOE of less than 100 for short- and intermediate-term exposure. 

Occupational Handlers 

HED conducted occupational exposure calculations in 1991 based on two dithiopyr studies: a 

Page 5 of 10 
passive dosimetry and biological monitoring study. While those studies were classified as 

"supplementary", data from the biological monitoring study was used to estimate Margins of 

Exposure (MOEs); MOEs were estimated to be greater than 100 (and therefore "not of concern") 

for occupational handlers. 

A revised occupational handler risk assessment may be needed for dithiopyr. Updated 

occupational handler exposure assessment may be required under registration review based upon 

revisions to the scenario-specific surrogate handler exposure data changes in toxicological 

endpoint selection. Furthermore, Agency reviews of the two occupational applicator studies 

used for estimating occupational exposure and risk noted a number of methodological 

deficiencies in the studies. 

Occupational Post-Application 

A revised occupational post-application risk assessment may be needed for dithiopyr. There is a 

possibility for workers to have post-application dermal exposure to dithiopyr treated turf 

following its uses. A chemical-specific transferable turf residue study is available, although the 

Agency identified substantive methodological issues in the 1991 study review. Given the age of 

the available study and the methodological issues noted in the Agency reviews, HED used 

screening methods to evaluate the need for a chemical-specific TIR study. 

Tur.fTrans.ferable Residue (7TR): Based on the discussion in the residential post-application 

section, a TTR study will not be required for Registration Review since estimated dermal MOEs 

for all occupational post-application scenarios are greater than 1 OX the LOC (i.e., calculated 

MOEs of 1 000). If the use pattern and/or toxicological points of departure change in the future, 

this requirement may be revisited. 

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

exposure assessment has not been performed for dithiopyr. However, there are multiple 

potential sources of post-application inhalation exposure to individuals performing postapplication activities in previously treated fields. These potential sources include volatilization 

of pesticides and resuspension of dusts and/or particulates that contain pesticides. The Agency 

sought expert advice and input on issues related to volatilization of pesticides from its Federal 

Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009. 

The Agency received the SAP's final report on March 2, 20101

• The Agency is in the process of 

evaluating the SAP report as well as available post-application inhalation exposure data 

generated by the Agricultural Reentry Task Force and may, as appropriate, develop policies and 

procedures to identify the need for and, subsequently, the way to incorporate occupational postapplication inhalation exposure into the Agency's risk assessments. If new policies or 

procedures are put into place, the Agency may revisit the need for a quantitative occupational 

post-application inhalation exposure assessment for dithiopyr. 

Conclusions: There is sufficient information available to assess occupational handler and postapplication exposures, although not all relevant occupational exposure scenarios were assessed in 

the last Agency risk assessment ( 1991) based on current ORE policies. During registration 

review, HED will consider the need for handler and post-application occupational assessments to 

1 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120 I 09meeting.html 

Page 6 of 10 
account for these policy changes; if a new assessment is needed, potential changes to the 

endpoints and safety factors will be included. 

Public Health and Pesticide Epidemiology Data 

The evaluation of the OPP Main Incident Data System (IDS) indicated 4 incidents identified in 

the United States from January 1, 2008, through June 11, 2013, for the single chemical dithiopyr, 

plus 8 additional incidents involving dithiopyr plus more than one chemical. In Aggregate IDS, 

from January I, 2008 to June 11, 2013, there were 108 incidents reported for dithiopyr. For 

dithiopyr, there appears to be a low potential for exposure. Dithiopyr is not included in the 

Agricultural Health Study (AHS), and therefore, does not provide information for this report. 

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. 

Cumulative 

The Food Quality Protection Act (FQPA) requires the Agency to consider the cumulative risks of 

chemicals sharing a common mechanism of toxicity. Dithiopyr is a member of the substituted 

pyridine class of pesticides. This class also includes fluroxypyr, imazapyr, thiazopyr, and 

triclopyr. Although the various pyridine herbicides have similar structural components, HED has 

not made a determination that they have a common mode of toxic action. Therefore, a 

cumulative risk assessment has not been performed for these compounds. 

Human Studies 

The previous risk assessments rely in part on data from studies in which adult human subjects 

were intentionally exposed to a pesticide or other chemical. These studies, which comprise the 

PHED, the Outdoor Residential Exposure Task Force (ORETF), and the Agricultural Reentry 

Task Force (ARTF), have been determined to require a review of their ethical conduct, and have 

received that review. 

Beyond the generic pesticide exposure database studies, there were two data reviews for 

chemical-specific dithiopyr occupational exposure studies; a passive dosimetry study and a 

biomonitoring study for lawn care applicators handling dithiopyr. HED intends to submit those 

two exposure studies for OPP ethics review during the registration review process. 

Data Needs and Risk Assessment Updates 

• Subchronic inhalation toxicity study 

• ToxSAC Meeting for endpoint selection 

• Dietary exposure assessment to include drinking water 

• Occupational/residential exposure assessment 

Page7of10 
References 

Author Barcode/MRID Date Title 

Dithiopyr: Summary of the Hazard and Science Policy Council 

November (HASPOC) Meeting of November 7, 2013: Recommendations on 

J. Leshin TXR 0056812 19,2013 the Requirement of a Subchronic Inhalation Study, an 

Immunotoxicity Study, a.nd the Acute and Subchronic 

Neurotoxicity Studies for Dithiopyr. 

E. Evans and 0415250 September Dithiopyr: Review of Human Incidents S. Recore 24,2013 

J.B. Stokes D169452 July 30, Dithiopyr in/on Imported Brown Rice. Evaluation of Analytical 

1992 Method and Residue Data. 

P. Chin and TXR #010631 October 13, Carcinogenicity Peer Review of Dithiopyr. E. Rinde 1993 

G.Z. Ghali TXR #012243 May29, RID/Peer Review Report ofDithopyr. 1997 

S.B. Mathur 0334268 Aprill6, FEE: Product Chemistry Review on Dithiopyr Technical. 2007 

Chow, Flora N/A March, Risk Assessment for Dithiopyr 

R044377 1991 

Schlosser, August, Evaluation of Monsanto Response to OREB Review of the Passive 

Arthur R118561 1992 Dosimetry Portion of Applicator Exposure Study of Dithiopyr Use 

on Lawns 

James D ... September .. . Post Application Exposure to Dithiopyr ... 

Rl48135 29, 1994 

Note: ellipse denotes illegible text. 

Websites 

http://chem.sis.nlm.nih.gov/chemidplus/cas/97886-45-8 

http://www.epa.gov/pesticides/science/residential-exposure-sop.html 

htto://www.eoa.swv/scioolv/SAP/meetin!:!s/2009/120109meeting.html 

http://www.eh.doe.Q.ov/neoa/tools/!!uidanceNolumel/2-6-EO 12898enviustice.pdf 

http://www.eoa.Qov/endo/ 

Page 8 of 10 
Attachment 1: Chemical Identity Table 

Chemicalldentity of Dithiopyr. 

Structure 

IUPACName 

N 

~ 

S,S'-dimethyl 2-ditluoromethyl-4-isobutyl-6-

tritluoromethylpyridine-3,5-dicarbothioate 

S,S'-dimethyl 2-(ditluoromethyl)-4-(2-methylpropyl)- Reference: 

CAS Name 6-(trifluoromethyl)-3,5-pyridinedicarbothioate 0334268, S. lt-C~o-m_m_o_n_N_a_m_e--------+--------"--0-it-h•...;..o...;..pyr -------~ Mathur, 16-APRI~----~--~------------~----------------~------------~2007 Molecular Formula C151-1 16F5N02S2 

Molecular Weight 401.40 glmole 

CAS Registry Number 97886-45-8 

PC Code Number 128994 

Physical State Powder 

Density 0.593 ± 0.005 glmL @20"C [Tap method] 

Color Tan 

Odor Characteristic of sulfur containing compounds 

Melting Point 65°C 

UV/Vis 254 nm 

pH 5.66@ 20"C 

Henry's Law Constant 1.51 x I 0..() atm-m3/mol @25"C Reference: 

II-V-ap_o.;_r_P-re-s-su_r_e --------+------4-_-0_x_I_O'""",-b_m_•_n_H @-::-2.::.5",--,,..-----~ http://chem.sis. n I 

l~-"-------------1 --------,..-,..-,-"--=---------l m.nih.gov/chemi 

II-L_o....;g;....K_o_w________ --1 _________ 4_·7_5 ________ --t dplus/cas/97886-

Water solubility 1.4 mg!L @20"C 45-8 

lie Acid. 

HOOC COOH 

Page 9 of 10 
Attachment 2. Dithiopyr Use Products and Sites Summary 

Attachment 2. Representative Use Patterns of Sec. 3/24C End-use Product Formulations of Dithiopyr. 

Registered Use Sites and Applicat.ion products & %AI Applicable ORE Reviews equipment Comments 

Formul. Types 

84886-3 0.08 

granular .25 lb Residential turf Drop spreader 

ai/acre 

Established lawns Ground Turf areas equipment, Industrial sites 81927- 10 0.625 lb Golf course turf Hand wand, No 

WSB ail acre Nonbearing fruit and nut trees backpack, chemigation 

handgun 

73327-5 .2 

granular .25 lb Residential turf Drop spreader 

ai/acre 

73327-6 .17 

granular 

.25 lb Residential turf Drop spreader 

ai/acre 

Conflicting 

Established lawns rate 

66222-213 40 Turf information 

WSB .625 lb Ornamental landscapes -listed as 

ail acre Nonbearing fruit and nut trees 0.5 and .625 

in different 

places 

Established lawns Ground 

12.7 Turf equipment, 

62719-426 0.5 lb Ornamental landscapes Hand wand, No 

EC ai/acre Nonbearing fruit and nut trees backpack, chemigation 

handgun 

Established lawns 

53883-208 .25 Turf Drop spreader 

granular .5 lb ai/A Ornamental landscapes 

Illegible 

32802-69 label 

Page 10 of 10