1 UNITED STATES ENVIRONMEN TAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

MEMORANDUM

DATE: 25 FEBRUARY 2008

SUBJECT: d-Limonene Occupational Exposure/Risk Assessment for Proposed New Uses of d-Limonene on Tree, Nut, Vine, Berry Crops and Non-Crop

Areas.

PC Code: 079701 DP Code: 348549

FROM: Mark I. Dow, Ph.D., Biologist Alternate Risk Integration Assessment Team (ARIA) Risk Integration Minor Use & Em ergency Response Branch (RIMUERB) Registration Division (RD) 7505P

THROUGH: John C. Redden, ARIA Team Leader

RIMUERB/RD 7505P

TO: Dana Vogel, Branch Chief Registration Action Branch 1 (RAB1)

Health Effects Division 7509P

INTRODUCTION

Under provisions in Section 3 of the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), as amended, Cutting Edge Formulati ons, Inc. has requested registration of the herbicide d-limonene. According to the draf t label it is intended for use around “tree, vine and berry crops (including, but not limited to : small fruits and berries, citrus fruits, pome fruits, stone fruits, subt ropical fruits, tree nuts, oliv es, grapes, kiwis and hops)....” The proposed product, GreenMatch, TM “may be applied between rows, on berms and for general weed control through initial fruit set and afte r the last harvest.”

Also according to the draft label, d-limone ne is requested for use on “Non-Crop Areas” which includes “borders, driveways, sidewa lks, around mature landscaping trees, shrubs, foliage and ornamentals, around buildings , in greenhouses and nurseries, and around

flower beds.”2 This memorandum serves as the ARIA/RD's assessment of exposure and risk to occupational pesticide handlers (mixers, loaders, applicators) and to agricultural workers.

It should be noted that the risk assessment t echniques used in this document are those that have been developed and refined by the Health Effects Divi sion (HED)/Office of Pesticide Programs' Science Policy Council fo r Exposure (ExpoSAC). Therefore, the risk assessment methods are the same as those used by HED and are HED standard operating procedure (SOP).

USE PATTERN SUMMARY

The use pattern summary is taken from: “GreenMatch Label, Version 1C, December 2007.” The product requested fo r registration is GreenMatch TM Organic Burndown

Herbicide. GreenMatch TM (GM) is intended for the cont rol of grasses and broadleaf weeds (annual and perennial) in crop and non-crop areas.

GM is a liquid formulation which contains 4.1 lb active ingredient (ai) d-limonene per gallon (55 % ai/gallon). Rates of application vary; for “small weeds” the rate is 14 % (14 gal GM/100 gal spray), for “larger weeds” th e rate is 18 % (18 gal GM/100 gal spray) and for “hard to control weeds” (such as ivy or hard to control perennials) the rate is 25 % (25 gal GM/100 gal spray). The label states: “A minimum spray volume of 60 gallons per acre is recommended.”

For the highest rate of a pplication: 25 gal GM * 4.1 lb ai/gal = 102.5 lb ai/100 gal finish spray or 1.025 lb ai/gal finish spray.

At a minimum spray volume of 60 gallons per acre: 1.025 lb ai/gal finish spray * 60 gal finish spray/A = 61.5 lb ai/A

There is a maximum of 15 gallons GM per acre (15 gal/A * 4.1 lb ai/gal = 61.5 lb ai/A). There is a maximum of 4 applications per year (246 lb ai/A/yr).

GM may not be applied through any type of irrigation system and may not be applied aerially. The label also stat es: “Do not use mist blower s or any other application techniques which may result in drift on to desirable vegeta tion. “ “Do not allow spray solution to drip, splash or dr ift on to desirable vegetation; small amounts can cause severe damage to crops.” “Avoid contact of herbic ide solution, spray drift or mist with foliage, green bark of trunk or branches, fruit or othe r parts of tees [sic], canes and vines.

The label directs: “Spray until thoroughly wet. ” Because the undersides of weed leaves may be more susceptible, side sprayi ng is recommended. Hooded sprayers are recommended as are low ground speeds and low spray pressures.

Applicators and other handlers are required to wear personal protective equipment (PPE) consisting of a long-sleeved shirt, long pants, shoes plus socks and protective eyewear.

The draft label lists a 4 hour restri cted entry interval (REI).3 See Table 1.0 for a summary of the proposed use pattern.

Table 1.0 Summary of Proposed Use Pattern for d-limonene on Non-Crop Areas

Formulation GreenMatch TM Organic Burndown Herbicide; 4.1 lb ai/gallon liquid; 55.0 % ai; EPA File Symbol 82052-A Sites/Crops tree, vine and berry crops (including, but not limited to: small fruits and berries, citrus fruits, pome fruits, stone fruits, subtropical fruits, tree nuts, olives, grapes, kiwis and hops);

Non-Crop Areas which includes borders, driveways, sidewalks, around mature landscaping trees, shrubs, foliage and ornamentals, around buildings, in greenhouses and nurseries, and around flower beds. Pest Annual and perennial weeds including grasses and

broadleaves Method of Applic. Ground-boom, low pre ssure hand wand; hand held pump up sprayer; backpack sprayer Max. Applic. Rate 15 gallons GM/A (61.5 lbs ai/A) Max. No. Applications 4/year Applic. Interval Not stated Preharvest Interval not applicable for non crop areas Restricted Entry Interval 4 hours listed on the label Manufacturer Cutting Edge Formulations, Inc.

OCCUPATIONAL PESTICID E HANDLER EXPOSURE

Based upon the proposed use patterns, ARIA/R D believes the most likely methods of application will be by ground-boom spray mach inery, low pressure hand-wand sprayer, backpack sprayer and hand-held pump-up spraye r. ARIA/RD further believes that for the proposed new uses, the most highly expos ed occupational pesticide handlers will be mixer/loaders using open-pour loading of li quid formulations, applicators using opencab, ground-boom sprayers, mixer/loader/appl icators using low- pressure hand-wand sprayers and backpack sprayers.

It is possible that some handlers might use hand-held pump-up sprayers. By comparison, the volume of spray material handled per day would be much smaller for hand-held pump-up sprayers than for the other methods a ssessed. Exposure and risk from the use of hand-held, pump-up sprayers is not expected to be greater than what is estimated for the

methods assessed.

Exposure durations are expected to be short- term duration (1-30 days). More than 1 short-term exposures may occur. However, si nce treatment blocks are generally expected to be comparatively small, intermediate-ter m (1-6 months) exposures are not expected, even for commercial applicators.

Particularly for ground a pplications, private ( i.e., grower) applicators may perform all functions, that is, mix, load and apply the material. The HED ExpoSAC procedure is4 such that although the same individual may perfor m all those tasks, they shall be assessed separately. The available exposure data for combined mixer/loader/applicator scenarios are limited in comparison to the monitoring of these two activities separately. These exposure scenarios are outlined in the Pest icide Handler Exposure Database (PHED) Surrogate Exposure Guide (August 1998). HED has adopted a methodology to present the exposure and risk estimates separately for the job functions in some scenarios and to present them as combined in other cases. Most exposure scenarios for hand-held equipment (such as hand wands, backpack sp rayers, and push-type granular spreaders) are assessed as a combined job function. With these types of hand held operations, all handling activities are assumed to be conducte d by the same individual. The available monitoring data support this and HED presen ts them in this way. Conversely, for equipment types such as fixed-wing aircraft , groundboom tractors, or air-blast sprayers, the applicator exposures are assessed and pres ented separately from those of the mixers and loaders. By separating the job functi ons, HED determines the most appropriate levels of personal protective equipment (PPE) for each aspect of the job without requiring an applicator to wear unnecessary PPE that might be required for a mixer/loader ( e.g., chemical resistant gloves may only be n ecessary during the pouring of a liquid formulation).

No chemical specific data were available w ith which to assess potential exposure to pesticide handlers. The estimates of exposur e to pesticide handlers are based, in part, upon surrogate study data available in the PH ED (v. 1.1, 1998). They are also based upon study data from the Outdoor Residen tial Exposure Taskforce (ORETF).

For pesticide handlers, it is HED standard practice to present estimates of dermal exposure for “baseline” that is, for worker s wearing a single layer of work clothing consisting of a long sleeved shirt, long pants, shoes plus socks and no protective gloves

as well as for “baseline” and the use of protective gloves or other PPE as might be necessary. Label required PPE was discussed earlier.

The toxicological factors used for risk a ssessment purposes are taken from: “Exposure

and Risk Assessment on Lower Risk Pesticid e Chemicals - - D-Limonene” prepared by the Special Review and Reregistration Divisi on, Office of Pesticide Programs, U.S. EPA (24 JAN 2005).

In the RED document, the Agency determined that for short-term duration (1-30 days) dermal and inhalation exposures the Lowest Observable Adverse Effect Level (LOAEL) of 400.0 mg ai/kg bw/day should be used to calculate risk. The toxic effects observed were liver effects (increased enzymes and liv er weights) seen in a 30-day rat gavage study. Since the toxicological endpoint is a LOAEL (not a No Observable Adverse Effect Level), an additional 3X uncertainty must be applied. Therefore, a Margin of Exposure of at least 300 is necessary to pr otect occupational pesticide handlers from short-term exposures to d-limonene as described by the product label.

However, upon reconsideration of the toxicological data , the RAB1 toxicology team

notes that the chronic RfD is slightly higher (i.e., more cons ervative) than the short-term5 exposure based on the same effect, the cRfD is considered protective of all exposure

scenarios. Therefore, in this assessment, the RAB1 toxicology team recommends using the NOAEL of 160 mg ai/kg bw/day to assess short-term duration inhalation and dermal exposures with a MOE of 100 (P.V. Shah, personal communication, February 2008). Since a NOAEL is used fo r risk calculations, a Margin of Exposure ≥ 100 is adequate to protect occupatio nal pesticide handlers. A body weight of 70 kg is used to calculate exposures to occupationa l pesticide handlers. See Table 2.0 for a summary of estimated exposures and risk to occupational pesticide handlers.

Table 2.0 Estimated Handler Exposure and Risk from the Proposed Uses of d-Limonene

Unit Exposure 1
mg a.i./lb handled Applic.

Rate 2 Units

Treated 3

Per Day Average Daily

Dose 4
mg a.i./kg bw/day NOAEL 5
mg a.i./kg bw/day MOE 6

SHORT-TERM

Mixer/Loader - Liquid - Open-pour

Dermal:

SLNoGlove 2.9

SLWGloves 0.023

Inhal 0.0012 61.5 lb

ai/A 40 A/day SLNoGlove 101.9

SLWGlove 0.8

Inhal 0.042 160 SLNoGlove

1.6

SLWGlove

190

Applicator - Ground-boom - Open Cab

Dermal:

SLNoGlove 0.014

SLWGloves 0.014

Inhal 0.00074 61.5 lb

ai/A 40 A/day SLNoGlove 0.49

SLWGlove 0.49

Inhal 0.026 160 SLNoGlove

310

SLWGlove

310

Mixer/Loader/Applicator Low-Pressure Hand-Wand SprayerLiquid Open Pour

Dermal:

SLNoGlove 100.00

SLWGloves 0.43

Inhal 0.03 1.02 lb ai/gal 40 gal/day

(41 lb ai/day) SLNoGlove 58.6

SLWGloves 0.25

Inhal 0.018 160 SLNoGlove

2.7

SLWGloves

597

Mixer/Loader/Applicator/Backpack Sprayer

Dermal:

SLNoGlove no data

SLWGloves 2.5

Inhal 0.03 1.02 lb ai/gal 40 gal/day

(41 lb ai/day) SLNoGlove no data

SLWGloves 1.46

Inhal 0.018 160 SLNoGlove

no data

SLWGloves

108

1. Unit Exposures are taken from “PHED SURROGATE EXPOSURE GUIDE”, Estimates of Worker Exposure from The Pesticide Handler Exposure Database Version 1.1, A ugust 1998. Dermal: SLNoGlove = Single la yer work clothing (long pants, long-sleeved shirt, shoes plus socks) No gloves; SLWG loves = single layer work clothing WITH the use of protective gloves; Inhal. = Inha lation. Units = mg a.i./pound of active ingredient handled 2. Applic. Rate. = Taken from draft GreenMatch label 3. Units Treated are taken from “Standard Values for Daily Acre s Treated in Agriculture”; SOP No. 9.1. ExpoSAC; Revised 5 July 2000; * Units Treated for hand held pump up sprayer adapte d from ExpoSAC SOP No. 12 Revised 22 FEB 01, Recommended Revisions to the Standard Operating Procedures (SOPs) for Residential Exposure Assessments. 4. Average Daily Dose = Unit Exposure * Applic. Rate * Units Treated * absorption factor (100 % absorption via dermal and inhalation) ÷ Body Weight ( 70 kg). 5. NOAEL = No Observable Adverse Effect Level 160 mg a.i./kg bw/day for short-te rm dermal and inhalation 6. MOE = Margin of Exposure = NOAEL ÷ ADD.6 A MOE of 100 is adequate to protect occ upational pesticide handlers from short-term exposures to d-limonene. Except for mixer/lo ader/applicators using backpack sprayers, all MOEs are > 100, provided handlers wear protective gloves which are NOT listed

on the label as PPE.

POST-APPLICATION EXPOSURE TO AGRICULTURAL WORKERS

It is possible for agricultural workers to have post-application e xposures to pesticide residues during the course of typi cal agricultural activities. In this case and for these use patterns, post-application expos ure is expected to be neg ligible. Sprays should not contact any crop areas (i.e. in a greenhouse or around ornamentals). Contact with treated foliage is not expected. Scouting for pest icide efficacy does not require contact with treated areas. Walking in treated areas se veral days post-application does not require

contact with treated surfaces ex cept for soles of shoes or boots thus exposure is not expected.

In addition, according to the RED document, th e vapor pressure of d-limonene is 2 mm Hg at 20 o C. As such, it is expected to volatili ze comparatively quickly. Therefore, a post-application exposure assessm ent was not conducted here.

RESIDENTIAL EXPOSURE

The label statements related to some of the noncrop areas could suggest use in residential settings (ie., borders, driveways, sidewalks, around mature landscaping trees, shrubs, foliage and ornamentals, around buildings). Based on the use instruction and general “tone” of the label, ARIA/RD believes the product is designed/intended for commercial/industrial use. Although, there is nothing that would preclude use by homeowners. If the product is applied ar ound residential settings, th ere is the possibility of post-application exposures to residents. The HED E xpoSAC believes residential postapplication exposure to treated ornamentals plantings is negligible and therefore it is not assessed. Materials applied to ho me lawns are routinely assessed.

cc:M.Dow(RIMUERB) RDI:J. Redden, N. Taydayon, M. Rust M.I.Dow:S7824:PY1:(703)305-5533:RIMUERB:7505P