UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460



### MEMORANDUM Date: April17, 2014 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION



### SUBJECT: Dithiopyr. Health Effects Division Response to Comments from Dow AgroSciences onthe U.S. EPA Dithiopyr Registration Review Docket [EPA-HQOPP-2013-0750]. 

### PC Code: 128994 

### Decision No.: 488638 

### Petition No.: N/A 

### DP Barcode: D418545 

### Registration No.: N/A 

### RegulatoryAction: Response to Comments 

### Case No.: N/A 

### RiskAssessment Type: N/ A TXRNo.: N/A 

### CAS No.: 97886-45-8 40 

### CFR: N/A 

### MRID No.: N/A
William Donovan, Ph.D., Chemist &

# Ri**~ .~.lill'i:.or** **W~ftv u~**  John Liccione, Ph.D.,**Toxicologisf7)? ~**  Matthew Lloyd, CIH; ORE Assessck'**·~** Risk Assessment Branches V & VII (RABVNII) 

### FROM:

Health Effects Division (HED) (7509P) 

### THROUGH: Michael Metzger, Chief

# ~(/ /) /) 

# d Risk Assessment Branches V & VII (RAB

## ~~ /· Health Effects Division (7509P) 

### TO: Veronica Dutch, Chemical Review Manager Risk Management and Implementation BranchV Pesticide Re-Evaluation Division (PRD) (7508P)
Attached are HED's responses to DowAgroSciences' (DAS's) Comments onU.S. EPA's Dithiopyr Registration Review Docket [EPA-HQ-OPP-2013-0750] dated February 17, 2014 regarding the dithiopyr Preliminary Work Plan (PWP).

Page 1 of4DOW Agro Sciences LLC Comment: #1 

### -Formulation type. "PrimaryDAS end use products containing dithiopyr are EW (emulsion in water) and granular formulations. These two formulations comprise the majority ofproduct sales associated withDAS dithiopyr registrations. EC, SC and WP/WSP formulations are also associated withDAS dithiopyr registrations."

EPA Response: HED thanks DowAgroSciences LLC (DAS) for the comments and will identify the DAS dithiopyr formulation types as Emulsion in Water (EW), granular (G), Emulsifiable Concentrate (EC), Soluble Concentrate (SC), and wettable powder/water soluble bag (WP/WSP) DOWAgro Sciences LLC Comment: 

### #2- Inhalation Study Requirement. "As dithiopyr specialtyherbicide provides preemergence control ofannual grasses and broadleafweeds in areas planted with tolerant ornamental plants listed on the label [13], exposure may be possible in the case ofhand-weeding oftreated areas. 

### In such cases 30 em is a reasonable height from the treated soil in which inhalation ofvapor phase dithiopyr maybe possible. The volatility ofa solid or liquid is defined by its vapor pressure (VP). The VP ofdithiopyr at 25°C is approximately 5.3 x 104 Pa (4.0 x 10-6 nun Hg). A saturated vapor atmosphere is achieved whenthe concentration ofsubstance in the gaseous phase is in equilibrium with the solid (or liquid) phase ofthe substance. The theoretical saturated vapor concentration (SVC) can be calculated based on the VP at a specific temperature and the atmospheric pressure. For dithiopyr, the calculated \theoretical) SVC at 25°C and sea level (760 nun Hg) would equal approximately 86.2 ug/m as determined bythe ideal gas law SVC = (VP)/(R*T), where R is the universal gas constant and T is temperature 

### COK). It is extremelyunlikely that this concentration could be achieved in the field because ofdilution in formulations and mass transfer limitations during evaporation from reactive surfaces and certainly not offsite when atmospheric dispersion and dilution are factored in. Concentrations ofdithiopyr have been measured directly over treated fields and in close proximityto numerous treated fields in a volatility study, conducted with an application rate of 1 lb/ac (2x the current maximum label rate) [7] which shows thatthe maximum concentration ofdithiopyr observed 30 em above the soil surface, directly overthe treated field is 7.82 ug/m3

, or less than 10% ofthe SVC. This is consistentwiththe EPA SAP's [8] comments; "Volatileflux.from crops will result in concentrations that are substantially below the saturation vaporpressure of mostvapors." Therefore using the SVC ofdithiopyr as the exposure endpoint for an inhalationrisk assessment would result in a protective assessment. Assuming that a human was exposed to the maximum observed concentration ofdithiopyr observed at 30.5 em above ground surface in a treated field (7.82 ug!m\ (areasonable worst-case assumption for post- application inhalation exposure during activities such as hand weeding), the exposure in mglkg/d would be determined by: mglkg/day = mg/Liday x absorption x conversion factor x duration ofexposure x activity factor

. Assuming: 100% absorption, Conversion factor= 47 [respiratoryvolume of7.15 Llhr +Bodyweight (0.152
Page 2 of4kg)], Activity factor= 1 (animal default), Duration= 6 hours (typical for repeat inhalation tox study), Mg/kg/day = 0.36 = most conservativeNOAEL from chronic dithiopyr study, Mg/L = 0.36/(47*6) = 1.28 x10-3 mg/L *1000L/1m3 = 1.28 mg/m3 * 1000 Jlg/mg = 1280 Jlg/m3

. Therefore, the SVC (86

.2 ug/m3) is 15-fold lower thanthe calculated exposure based on the NOAEL (1280 Jlg/m3)

. Additionally,more realistically, the maximum concentration observed (7.82 ug!m\ is 164-fold lower than the calculated exposure based on the NOAEL (1280 Jlg/m3 ). Finally, a more refined exposure assessment indicates that the maximum concentration at the breathing height (1.83 m) directly overthe treated field is 1.06 ug/m3• As suchthis represents a 1200-fold lower exposure than the 1280 Jlg/m3concentration based on the NOAEL of0.36 m/k/d

. The margins ofsafety estimated here would be even larger ifthe air concentration estimates had been obtained from a field volatility study conducted atthe current maximum label rate of0.5 lb/ac, instead of 1lb/ac.
DowAgroSciences supports the EPA determination that the requirements for the acute and subchronic neurotoxcity as well as immunotoxicity studies should be waived based on the existing toxicity database for dithiopyr. We would like to better understand the exposure scenario in question leading to the request for a subchronic inhalation study. Ifit can be concluded based on conservative assumptions that conducting a subchronic inhalation study would be unlikelyto provide new information useful for risk assessment then we will provide further rationale to petition that this request be waived. Briefly, the potential for exposure to dithiopyr vapor does not appeartojustifythe conduct ofthis study. As discussed, a saturated atmosphere would be approximately 15 fold lowerthanthe most conservative availableNOEL [converted to exposure concentration] and 164 fold lower than a realistic exposure concentration. Conducting a repeated exposure inhalation study even at a saturated concentrationthus would be unlikely to yield any hazard or effects that would be relevant to risk assessment."

EPA Response: HED thanks DAS for the clear description ofthe dithiopyr use patterns and for providing their rationale onwhy an inhalation study should not be required for dithiopyr

. HED also notes DAS support for data waivers for the following: the acute and chronic neurotoxicity studies, and the immunotoxicity study. HED's Hazard and Science Policy Council (HASPOC) determines the necessity for inhalation studies (in this case, a subchronic inhalation study) based on a weight ofevidence (WOE) approach that includes physical-chemical properties, use pattern and exposure scenarios, screening margins ofexposure (MOEs), and toxicity. Based on informationprovided in the DAS comments and updates to the screening inhalation risk estimates to reflect updated application rate information, the HASPOC is currently reconsidering its previous decision to require a subchronic inhalation study for dithiopyr. The results ofthis reconsideration are expected be available in due course.

Page 3 of4DOWAgro Sciences LLC Comment: #3 

### -Residential BystanderAssessment. "There is not an agricultural use pattern established for dithiopyr, as stated in the Occupational Exposure section ofthe Human Health Assessment Scoping Document (Page 5). A single maximum application rate of0.5 lb a.i./acre exists for all DAS registrations containing dithiopyr."

EPA Response: HED concurs with DAS that there is no established agricultural use pattern. However, there are a number ofregistered non-agricultural use sites (e.g., roadsides, utility rightof-ways, railways, non-cropland, and industrial areas) thatmay receive broadcast treatments of dithiopyr for control ofannual grasses and/or broadleafweeds. Regardless ofwhetherthe intended application is for agricultural or non-agricultural use sites, HED intends to address residential exposures resulting from off-site transport (e.g., spray drift orvolatilization) that might occur as a result.ofdithiopyr applications. HED intends to address the potential for residential bystander exposure based onthe established dithiopyr use pattern to large broadcast areas like golfcourses and rights-ofway/industrial areas. HED acknowledges the maximum application rate of0.5 lb ail A for DAS dithiopyr products. Comment#4 (below) also addresses the dithiopyr application rate. DOW Agro Sciences LLC Comment: 

### #4- Dithiopyr application rate. "A single maximum application rate of0.5 lb a.i./acre exists for all DAS registrations containing dithiopyr. DAS does not know ofany dithiopyr federal productregistrations with a maximum application rate above 0.5 lb ailacre. DAS respectfullyrequests that risk assessments for DAS registrations are performed using the maximum applicationrate of0.5 lb ai/acre."
EPA Response: HED thanks DowAgroSciences LLC for the clarification onthe maximum applicationrate for DAS dithiopyrproducts. The majority ofdithiopyrproductlabels indicate a single maximum application rate ofno more than 0.5lb ai/A. HED notes that DAS is not the only registrant for dithiopyrproducts; while DAS dithiopyrproducts may be applied at a maximum rate of0.5 lb ai/A, HED uses the maximum single dithiopyr application rate from all registrants (0.875 lb ai/A) to evaluate occupational and bystander risk estimates.

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