UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

DATE: May27,2015 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

SUBJECT: Oxyfluorfen: Response to Comments on the HED Human Health Scoping 

Document. 

PC Code: I I 160 I DP Ba rcode: 0426 181 

Decision No.: 502380 

Petition No.: NA 

Registration No.: NA 

Regula tory Action: Registration Review Scoping 

Risk Assessment Type: NA Case No.: 2490 

TXR No.: NA CAS No.: 42874-03-3 

MRID No.: NA 40 CFR: § 180.38 1 

Ivan D. Nieves, Chemist/Risk Assessor 

Bonnie Cropp-Kohlligian, Environmental Sc nti s~' ~ -~ · ~ Thurston G. Mor1on, Chemist (4 /J ~v{!:. ~--· 

Risk Assessment Branch IV ~ ""' 

FROM: 

Health Effects Division (7509P) 

THROUGH: Charles Smith, Branch ChieL_ ~ ~ --

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TO: Benjamin Askin, Chemical Review Manager (RM 51) 

Risk Management and Implementation Branch IV 

Pesticide Re-Evaluation Division (7508P) 

Attached is HED's Response to Comment on the human health risk assessment scoping 

document for oxyfluorfen to support Registration Review. 

The HED Oxytluorfen Risk Assessment team has received comments on the Registration 

Review Scoping Document (EPA Docket ID: EPA-HQ-OPP-2014-0778). Comments relevant 

to HED's scoping document were provided by Dow AgroSciences and the City of Sacramento 

Department of Utilities. 

Page 1 of 4 
EPA'S RESPONSE TO COMMENTS FOR OXYFLUORFEN 

I. Introduction 

The following is EPA's response to public comments on the human-health assessment scoping 

document in support of Registration Review for oxyfluorfen. Some of the responses serve as 

clarification or a restatement of Agency policies and guidance and it is hoped that this will 

provide a greater understanding of the Agency's position and procedures on these matters. 

Comments concerning the rationale behind Agency decisions, toxicology, exposure assessment, 

and interpretation of available data, were submitted. 

11. Comments 

Dow AgroSciences 

A. Chemical Use Profile 

The Agency states on page 3 of 20: 

"Major uses include grapes, almonds, cot/on, bulb vegetables. artichokes and paslure/rangeland. " 

DAS Comment: 

The list of major uses should be corrected so that it reads: almonds, wine grapes, pistachios, and walnuts. 

Note that these crnps are also identified in the BEAD Review. [4] 

The Agency states on page 3 of 20: 

"Liquid formulations might be applied by using groundboOln, airblasl, chemigation, aerial and handheld 

sprayers. " 

DAS Comments: 

This list of application methods should be corrected so that it reads: Liquid formulations might be applied 

by using groundboom, chemigation, aerial and handheld sprayers. 

The Agency states on page 3 of 20: 

"Formulations include emulsifiable liquid products for agricultural use and granular products for 

commercial nursery use. " 

DAS Comment: 

This statement is incorrect and should be updated so that it reads: Formulations include emulsifiable 

concentrate and suspension concentrate liquid products for agricultural and nonagricultural use and 

granular products for commercial nursery use. 

HED Response: 

The Agency thanks Dow AgroSciences for their comments regarding HED's human-health risk 

assessment scoping document for oxyfluorfen related to the use pattern of oxyfluorfen. The 

Agency has considered these comments and will utilize them, along with any newly available 

data, during the Registration Review of oxyfluorfen. 

B. Risk Assessment Updates and Data Deficiencies 

The Agency states on page 11 of 20: 

A summmy of the toxicity data needs is presented which includes: Sub chronic Dermal Toxicity and 

Dislodgeable Foliar Residue 0 11 bulb vegetables. 

DAS Comment: 

In response to this request, DAS will submit the following: 

Page 2 of 4 
870.3200121128 - Day Derma l Toxicity 

Dow AgroSciences, LLC 

Report IO: NTB02 l 715 

Page 11 of 13 

Stebbins, K. E., et. al. (2002) Oxyjlu01fen: 28-Day Dermal Toxicity Study in Fischer 3./-1 

Rats. 

This report is referenced further herein as Stebbins (2002). 

Howeve r, DAS disagrees with the Agency's recommendations for the following: 

875.2100/ Dislodgeable Foliar Residue (bulb vegetable) 

Study results of Stebbins (2002) demonstrate that the systemic NOEL for oxyfluorfen administered via 

the dermal route is 1000 mg/kg bw/day, which is at the limit dose for this type of study. In the current 

assessment conducted by the EPA, defau lt DFR values were implemented to calculate workers' re-entry 

exposure for bulb vegetables. The margin of exposure (MOE) for the hand weeding activity (highest 

exposure scenario) was calculated to be 1,800. As part of the ca lculation a LOA EL va lue of 32 mg/kg 

bw/day based on liver toxicity and anaemia in a 90-day mouse oral study was used. DAS believes that the 

NOEL of 1.000 mg/kg bw/day generated from the 28-day dermal toxicity study in rat is the most relevant 

endpoint and should be used to generate a new MOE. As the new suitable NOEL from the rat dermal 

study is 3 I .25X higher than the old LOAEL from the mouse study it is recommended that the old 

MOE should be increased by the same factor, the va lue of which would now be: ( 1,000/32)* 1,800) = 

56250. If 18% derma l absorption was accounted for in generating the EPA's origina l MOE of 1800 then 

the new MOE of 56250 should be reduced to I 0125. The value of I 0125 is above the current level of 

concern (LOC) of 3000 used by the EPA for dermal intennediate-term exposures to oxyfluorfen. It is 

understood that this LOC is based on a combination of not only the standard inter- and intraspecies 

uncertainty ( I OOX) generated when using in vivo data to extrapolate to humans but also a factor of 3 for 

using a LOA EL rather than NOA EL and a database uncertainty factor of lOX used due to a paucity of 

route relevant toxicology data. The new data provided means that the LOC should be reduced to 

I 00 given that both the database uncerta inty factor and the LOA EL to NOAEL uncertainty factor need 

not be applied. Consequently, DAS recommends the need for the Dislodgeable Foliar Residue Study on 

bulb vegetable for oxyfluorfen to be reconsidered. 

HED Response: 

The Agency looks forward to the submittal o f the 28 day dermal tox icity study and the waiver 

request for the Dislodgeable Foliar Residue Study on bulb vegetable fo r oxyfluorfen. The Agency will 

review and utilize them (if adequate), during the Registration Review of oxyfluorfen. 

City of Sacramento Department of Utilities 

We appreciate that when EPA develops its registration review work plans, it considers the 

potential for the pesticide to affect drinking wate r quality. We would prefer that the endpoints in 

the human health effects assessment be more comprehensive than EPA currently uses in its 

pesticide reviews. While our primary conce rn is potential human health effects to our customers, 

we also have concerns about adverse taste and odor from pesticides and their breakdown 

products (through degradation and transformation) and cumulative and potentia l synergistic 

effects of exposure to multiple pesticides. 

We believe it is important for EPA to include the following additional considerations when 

evaluating human health risk from pesticides: 

Page 3 of 4 
Effects of the parent chemicals, metabolites, degradates, and transformation products formed 

during and subsequent to water treatment processes. 

Effects of water treatment processes on residue removal and on the creation of transformation 

products from the parent chemical. 

Cumulative and possible synergistic effects of pesticides and their breakdown products in 

drinking water. 

Estimation of the concentrations that might occur in downstream surface water, based on all 

pathways for release to surface waters, including drift. 

Require monitoring and data collection by pesticide registrants to support EPA's evaluation of 

the above. 

HED Response: 

The Agency considers all available information and data when conducting human health risk 

assessments. The Agency has considered these comments and will utilize them, along with any 

newly available data, during the Registration Review of oxyfluorfen. 

Page 4 of 4