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 on the U.S. EPA Dithiopyr Registration Review Docket [EPA-HQOPP-20 13-0750]. 

PC Code: 128994 

Decision No.: 488638 

Petition No.: N/A 

DP Barcode: D418545 

Registration No.: N/A 

Regulatory Action: Response to Comments 

Risk Assessment Type: N/ A Case No.: N/A 

TXRNo.: N/A CAS No.: 97886-45-8 

MRID No.: N/A 40 CFR: N/A 

John 

William 

Liccione, 

Donovan, 

Ph.D., 

Ph.D., 

Toxicologisf7)?

Chemist & Ri~ 

~ .~.lill'i:.or W~ftv u~ 

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 Branch V 

Pesticide Re-Evaluation Division (PRD) (7508P) 

Attached are HED's responses to Dow AgroSciences' (DAS's) Comments on U.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 of4 
DOW Agro Sciences LLC Comment: #1 -Formulation type. "Primary DAS end use products 

containing dithiopyr are EW (emulsion in water) and granular formulations. These two 

formulations comprise the majority of product sales associated with DAS dithiopyr 

registrations. EC, SC and WP/WSP formulations are also associated with DAS dithiopyr 

registrations." 

EPA Response: HED thanks Dow AgroSciences 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) 

DOW Agro Sciences LLC Comment: #2- Inhalation Study Requirement. "As dithiopyr 

specialty herbicide provides preemergence control of annual grasses and broadleaf weeds in 

areas planted with tolerant ornamental plants listed on the label [13], exposure may be possible 

in the case of hand-weeding of treated areas. In such cases 30 em is a reasonable height from 

the treated soil in which inhalation of vapor phase dithiopyr may be possible. 

The volatility of a solid or liquid is defined by its vapor pressure (VP). The VP of dithiopyr at 

25°C is approximately 5.3 x 104 Pa (4.0 x 10-6 nun Hg). A saturated vapor atmosphere is 

achieved when the concentration of substance in the gaseous phase is in equilibrium with the 

solid (or liquid) phase of the 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 by the ideal gas law SVC = (VP)/(R *T), where R is 

the universal gas constant and T is temperature COK). It is extremely unlikely that this 

concentration could be achieved in the field because of dilution in formulations and mass 

transfer limitations during evaporation from reactive surfaces and certainly not offsite when 

atmospheric dispersion and dilution are factored in. Concentrations of dithiopyr have been 

measured directly over treated fields and in close proximity to 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 that the maximum concentration of dithiopyr observed 30 em above the 

soil surface, directly over the treated field is 7.82 ug/m3

, or less than 10% of the SVC. This is 

consistent with the EPA SAP's [8] comments; "Volatileflux.from crops will result in 

concentrations that are substantially below the saturation vapor pressure of most vapors." 

Therefore using the SVC of dithiopyr as the exposure endpoint for an inhalation risk 

assessment would result in a protective assessment. Assuming that a human was exposed to 

the maximum observed concentration of dithiopyr observed at 30.5 em above ground surface in 

a treated field (7.82 ug!m\ (a reasonable 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 of exposure x 

activity factor. 

Assuming: 100% absorption, 

Conversion factor= 47 [respiratory volume of7.15 Llhr +Body weight (0.152 

Page 2 of4 
kg)], 

Activity factor= 1 (animal default), Duration= 6 hours (typical for repeat 

inhalation tox study), 

Mg/kg/day = 0.36 = most conservative NOAEL 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 than the 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 over the treated field is 1.06 ug/m3

• As 

such this represents a 1200-fold lower exposure than the 1280 Jlg/m3 concentration based on 

the NOAEL of0.36 m/k/d. The margins of safety estimated here would be even larger ifthe 

air concentration estimates had been obtained from a field volatility study conducted at the 

current maximum label rate of 0.5 lb/ac, instead of 1 lb/ac. 

Dow AgroSciences 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. If it can be 

concluded based on conservative assumptions that conducting a subchronic inhalation study 

would be unlikely to 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 appear to justify the conduct of this study. As discussed, a saturated 

atmosphere would be approximately 15 fold lower than the most conservative available NOEL 

[converted to exposure concentration] and 164 fold lower than a realistic exposure 

concentration. Conducting a repeated exposure inhalation study even at a saturated 

concentration thus 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 of the dithiopyr use patterns and for 

providing their rationale on why 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 of evidence (WOE) 

approach that includes physical-chemical properties, use pattern and exposure scenarios, 

screening margins of exposure (MOEs), and toxicity. Based on information provided 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 of this reconsideration are expected be 

available in due course. 

Page 3 of4 
DOW Agro Sciences LLC Comment: #3 -Residential Bystander Assessment. "There is not 

an agricultural use pattern established for dithiopyr, as stated in the Occupational Exposure 

section of the Human Health Assessment Scoping Document (Page 5). A single maximum 

application rate of 0.5 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 of registered non-agricultural use sites (e.g., roadsides, utility rightof-ways, railways, non-cropland, and industrial areas) that may receive broadcast treatments of 

dithiopyr for control of annual grasses and/or broadleaf weeds. Regardless of whether the 

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 or volatilization) that 

might occur as a result. of dithiopyr applications. HED intends to address the potential for 

residential bystander exposure based on the established dithiopyr use pattern to large broadcast 

areas like golf courses and rights-of way/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 of 0.5 lb a.i./acre exists for all DAS registrations containing dithiopyr. DAS 

does not know of any dithiopyr federal product registrations with a maximum application rate 

above 0.5 lb ailacre. DAS respectfully requests that risk assessments for DAS registrations are 

performed using the maximum application rate of0.5 lb ai/acre." 

EPA Response: HED thanks Dow AgroSciences LLC for the clarification on the maximum 

application rate for DAS dithiopyr products. The majority of dithiopyr product labels indicate 

a single maximum application rate of no more than 0.5lb ai/A. HED notes that DAS is not the 

only registrant for dithiopyr products; while DAS dithiopyr products 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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