Document ID: EPA-HQ-OPP-2011-0488-0005
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2012-12-10T05:00Z

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

                                                      OFFICE OF CHEMICAL SAFETY
                                                       AND POLLUTION PREVENTION

MEMORANDUM

DATE:	March 27, 2012

SUBJECT:	Tolclofos-methyl.  Occupational and Residential Exposure Assessment for Proposed Seed Treatment Uses on Various Crop Groups 
 
PC Code:  128905
DP Barcode:  D395997
Decision No.:  443921
Registration No.:  
Petition No.:  NA
Regulatory Action:  Section 3
Case No.:  NA
Risk Assessment Type:  Single Chemical
TXR No.:  NA
CAS No.:  57018-04-9
MRID No.:  NA
40 CFR:  

FROM:	Shalu Shelat, Industrial Hygienist 
	Risk Assessment Branch 6
	Health Effects Division (7509P)
	
THROUGH:	Charles Smith, Risk Assessor
	Risk Assessment Branch 6
	Health Effects Division (7509P)	

TO:	Lisa Jones/Mary Waller, Risk Management Team 21
	Herbicide Branch
	Registration Division (7505P)
	Risk Management Division
	
The Registration Division (RD) requested that the Health Effects Divison (HED) conduct an exposure and risk assessment for a new proposed seed treatment use of tolclofos-methyl on various crop groups including: Root and Tuber Vegetables (Crop Group 1, except potato, sweet potato, and yam bean); Bulb Vegetables (Crop Group 3-01); Leafy Vegetables (except brassica vegetables) (Crop Group 4); Brassica (Cole) Leafy Vegetables (Crop Group 5); Legume Vegetables (Succulent or Dried) (Crop Group 6); Fruiting Vegetables (Crop Group 8-10); Cucurbit Vegetables (Crop Group 9); Cereal Grains (Crop Group 15, except rice and wildrice); Grass Forage, Fodder, and Hay (Crop Group 17); Non-grass Animal Feeds (Forage, Fodder, Straw, and Hay) (Crop Group 18); Herbs and Spices (Crop Group 19); Oilseeds (Crop Group 20, except Cotton); Cotton; Ornamental Flowers; and Conifers. Note: This memorandum was reviewed by the Exposure Science Advisory Council (ExpoSAC) on 11/10/2011.
1.0	EXECUTIVE SUMMARY 

Tolclofos-methyl (O-(2,6-dichloro-4-methylphenyl) O-O-dimethyl phosphorothioate) is a new active ingredient which works as a contact fungicide formulated for seed treatment use to provide protection against seed-borne fungal pathogens causing seed decay and seedling damping-off.  Rizolex(TM) Flowable Fungicide contains 42% tolclofos-methyl (4.17 lbs ai per gallon) and is proposed to be used on various seed types. 

This document assesses the occupational exposure and risk estimates for the newly proposed seed treatment uses of tolclofos-methyl.  Based on application rate and label information, exposure is expected to occur for short- and intermediate-term durations.  Chronic exposure is not expected for the proposed use patterns.  

Proposed Use Profile
The proposed tolclofos-methyl application rates range from 0.00009773 to 0.000489 lb ai/lb seed for seed treatment.  Tolclofos-methyl seed treatment uses are to be applied utilizing mechanical, slurry, or mist-type seed treating equipment.  The product is proposed for both commercial seed treatment facilities and on-farm application, but is not allowed to be applied in  a hopper-box or planter-box at planting time.   The proposed label also states that the product is only to be applied to "true seeds" and is not to be applied on other propagation parts.  

Residential Exposure
Residential exposures and risk estimates are not assessed in this document because the proposed uses of tolclofos-methyl do not involve applications by homeowners or commercial applicators in residential settings at this time and there are no existing or proposed residential uses.

Occupational Handlers 
Occupational handler exposure is expected for individuals involved in commercial seed treatment (primary handlers) and planting treated seeds (secondary handlers).  Dermal risk estimates were not assessed for this use because systemic toxicity and dermal irritation was not observed at concentrations up to the limit dose (1,000 mg/kg/day) after 3 weeks of exposure (5 days/week for 3 weeks).  The inhalation risk estimates do not exceed HED's LOC (MOE >= 100) and therefore are not of concern to HED.  MOEs for all primary handler seed treatment activities ranged from 14,000 to 51,000,000 and MOEs for secondary handler activities planting treated seed ranged from 147,000 to 870,000,000. 

 Occupational Post-Application 
The potential for short- and intermediate-term occupational exposure to tolclofos-methyl during post-application activities is unlikely because sustained levels of contact with treated seed is not expected after the seed has been placed in the soil or other planting media.  Therefore, no quantitative post-application assessment is required for exposure to treated seeds that have already been planted.

Label Recommendations
The labeling should state:  Seed that has been treated with this product that is then packaged or bagged for future use must contain the following labeling on the outside of the seed package or bag. 
      "Treated Seed - Do Not Use for Food, Feed, or Oil Purposes. Store away from feeds and other foodstuffs.  
      When opening this bag or loading/pouring the treated seed, wear a long-sleeved shirt, long pants, shoes, socks, and chemical resistant gloves.  After the seeds have been planted, do not enter or allow worker entry into treated areas during the restricted-entry interval (REI) of 12 hours. Exception: Once the seeds are planted in soil or other planting media, the Worker Protection Standard allows workers to enter the treated area without restriction if there will be no worker contact with the treated seeds in the soil or planting media."

Review of Human Research
This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical.  These data, which include ExpoSAC Policy 14 (SOPs for Seed Treatment), are subject to ethics review pursuant to 40 CFR 26, have received that review, and are compliant with applicable ethics requirements.  For certain studies that review may have included review by the Human Studies Review Board.  Descriptions of data sources as well as guidance on their use can be found at http://www.epa.gov/pesticides/science/handler-exposure-data.html and http://www.epa.gov/pesticides/science/post-app-exposure-data.html.

2.0	HAZARD CHARACTERIZATION

Tolclofos-methyl is an organophosphate with several older toxicity studies (dating back to 1970s) submitted for consideration in risk assessment.  Upon re-evaluation of these old toxicity studies (1970s to 1980s), several studies are now considered unacceptable: 90-day oral rat (MRID No. 00156135) (1982); developmental rat (MRID No. 00156142) (1979); developmental rabbit (MRID No. 00156143) (1982); 3-generation reproduction (MRID No. 00156145) (1985); carcinogenicity mouse (MRID No.00156139) (1983), and chronic/carcinogenicity rat (MRID No. 00156140) (1982).  

Based on the re-evaluation of these old toxicity studies, the toxicity database for tolclofos-methyl is not complete but adequate for the proposed non-food seed treatment use. Data from the following studies were used to evaluate the hazard potential of tolclofos-methyl: 
- Acute lethality studies (oral, dermal, inhalation, primary eye and dermal irritation, dermal sensitization)
- Subchronic dietary (rat, dog)
- 9-month dietary (mouse)
- 104-week special Cholinesterase (rat)
- Developmental (rat, 41422904)
- Neurotoxicity (acute and subchronic) (rat)
- Metabolism (rat, mouse)
- Immunotoxicity (rat)
- Mutagenicty battery

Tolclofos-methyl is a new active ingredient although it has been registered in other countries (European Union countries) for several years.  A search in PubMed (August 2011) with tolclofos-methyl as a search term resulted in no applicable toxicity studies for risk assessment and no toxicity studies with humans were submitted.  Any future uses (other than seed treatment) requested by the registrant will require several new toxicity studies to fulfill the Revised Part 158 guidelines for either a non-food or a food use.  

Tolclofos-methyl has low acute toxicity by oral, dermal, and inhalation routes.  It is not a dermal sensitizer, or a skin or eye irritant.  The acute toxicity profiles of tolclofos-methyl are summarized in Table 1.

             Table 1. Acute Toxicity Profile for Tolclofos-methyl*
                                 Guideline No.
                                  Study Type
                                     MRID
                                    Results
                               Toxicity Category
                                       
                                   870.1100
                                Acute oral- rat
                               Acute oral-mouse
                                       
                                Acute oral-dog
                                00156124 (1985)
                                00156128 (1978)
                                       
                                00156125 (1978)
                      Combined LD50 > 5 g/kg, rats[#]
                         3500 mg/kg (2760-4800), mice
                                       
                              >1000 mg/kg/day
                                      IV
                                      III
                                       
                                      III
                                   870.1200
                             Acute dermal- rabbit
                                00156126 (1985)
                                 Water vehicle
                               1/5 died by day 5
             No clinical signs after dosing of surviving rabbits.
                               LD50 > 2 g/kg
                                      III
                                   870.1300
                           Acute inhalation  -  rat
                                     -rat
                              41410501 (1986)[@]
                      Powder,non-acceptable/non-guideline
                                       
                               41445702 (1983) @
                   25% flowable, unacceptable/non-guideline
                               LC50>= 3.32 mg/L
                             Particles 0.3-5.5um
                          %MMAD 1um or less not met
                                       
                              LC50>= 0.146 mg/L
                              MMAD not determined

                                       
                                      III
                                       
                                       
                                       
                                      NA
                                       
                                       
                                       
                                   870.2400
                        Primary eye irritation- rabbit
                                00156129 (1985)
 Transient slight conjunctival reaction (24 hrs or less). Not an eye irritant
                                      IV
                                       
                                   870.2500
                       Primary Dermal irritation- rabbit
                                00156131 (1985)
                            PIS=0, not an irritant
                                      IV
                                       
                                   870.2600
                        Skin sensitization- guinea pig
                                00156131 (1985)
                           Not a contact sensitizer
                                      N/A
*Acute summaries found in TXR006933
[#]Clinical signs (piloerection, hunched posture) in all animals were observed shortly after dosing with complete recovery by 5 days post-dosing.
[@]Studies found in TXR008856

In risk assessments for non-food uses that do not result in residential exposures, PODs are selected for the dermal and inhalation routes of exposure only.  In this case, there is no dermal toxicity and therefore a dermal POD has not been selected and a quantitative dermal assessment not performed.  A quantitative assessment was only performed for the inhalation route. PODs for the acute and chronic dietary and incidental oral exposures are not required to assess risk for non-food uses that do not result in residential exposures, and therefore have not been selected.

Acute and Chronic Dietary
The current proposed use is a non-food seed treatment.  Acute and chronic PODs have not been established for this risk assessment.

Short/Intermediate Dermal
The 21-day dermal rabbit study (non-guideline) was re-evaluated to ensure consistency with current HED policy and practices.  Based upon this re-evaluation, systemic toxicity and dermal irritation was not observed at concentrations up to the limit dose (1,000 mg/kg/day) after 3 weeks of exposure (5 days/week for 3 weeks).  Therefore a quantitative short- and intermediate-term dermal assessment has not been conducted for tolclofos-methyl.

Short/Intermediate Inhalation
The short- and intermediate-term inhalation POD was based on oral toxicity studies since route specific inhalation data are currently unavailable.  The 90-day rat and 6- month dog studies provide the most appropriate PODs to consider for risk assessment.  The 90-day rat and 6-month dog studies were selected as co-critical since they yield similar NOAELs and LOAELs for use in risk assessment.  The NOAEL of 23 mg/kg/day from the 6-month dog study, which is similar to the RBC BMDL10 of 34 mg/kg/day from the 90-day rat study, is the most appropriate POD and protective of the short-term and intermediate-term durations of exposure.  An uncertainty factor of 100x (10x to account for interspecies extrapolation and 10x for intraspecies variation) was applied to the POD.  This POD is considered health protective since the recently submitted ACN and SCN studies resulted in no ChE inhibition or toxicity near the limit dose of 1,000 mg/kg/day.

Carcinogenicity and Cancer Classification
There are no currently registered or proposed food uses for tolclofos-methyl.  Carcinogenicity studies are not required for non-food use chemicals.  Carcinogenicity studies in mice and rats are available for tolclofos-methyl and both of these studies were deemed unacceptable for use in the risk assessment.  These cancer studies would be required under the Revised Part 158 Guidelines should a food use for tolclofos-methyl be requested in the future.

Uncertainty Factors
Food Quality Protection Act (FQPA) considerations do not apply to tolclofos-methyl as the proposed seed treatment uses have been deemed non-food uses.  However, there are three outstanding studies according to revised 40 CFR Part 158 Toxicology Data Requirements.  These studies include a development toxicity study in rabbits, a reproduction study in rats, and an adequate in vivo mammalian cell assay.  The Agency is not requesting any of these studies at this time and does not believe a UFDB is required for the lack of these studies.  Based on the proposed uses, quantification of risk is limited to short- and intermediate-term inhalation exposure for workers.  The PoD used for assessing repeated inhalation exposure is based on the most sensitive endpoint in the most sensitive species (dogs) and supported by the observation of similar effects at a comparable dose in the rat.  Consequently, the risk assessment does not underestimate potential risks to occupational workers and a total uncertainty factor of 100 is adequate.

Table 2.0.  Summary of Toxicological Doses and Endpoints for Tolclofos-Methyl for Non-Food Use Occupational Risk Assessments
                                   Exposure/
                                   Scenario
                           Point of Departure (POD)
                              Uncertainty Factors
                               Level of Concern
                        Study and Toxicological Effects
Acute Dietary (General Population, including Infants and Children)
                 The proposed seed treatment use is non-food.
Chronic Dietary (All Populations)
                 The proposed seed treatment use is non-food.
Dermal (Short/Intermediate)
  Systemic toxicity was not observed up to the limit dose of 1,000 mg/kg/day.
Inhalation
(Short/Intermediate)
                                NOAEL= 23 mg/kg
UFA = 10X
UFH = 10X
                                   MOE = 100
Co-Critical:
1.  6-month dog  (00156138); 
LOAEL = 70 mg/kg/day, based on decreased bodyweight and gain, hematocrit, hemoglobin, and erythrocyte count in both sexes.  In addition, ↓relative thyroid weight, ↑ALK and ↑absolute and relative liver wt at high dose.
A consistent dose-response for ChE was not observed.
2. 90-day rat (41422901)
 RBC BMDL10=34 MKD
RBC BMD10=72 MKD
Cancer (oral, dermal, inhalation)
                   Not required for non-food use pesticides.
Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and  used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures.  NOAEL = no observed adverse effect level.  LOAEL = lowest observed adverse effect level.  UF = uncertainty factor.  UFA = extrapolation from animal to human (interspecies).  UFH = potential variation in sensitivity among members of the human population (intraspecies).

Food Quality Protection Act (FQPA) considerations do not apply to tolclofos-methyl as the proposed seed treatment uses have been deemed non-food uses.  However, there are three outstanding studies according to revised 40 CFR Part 158 Toxicology Data Requirements.  These studies include a development toxicity study in rabbits, a reproduction study in rats, and an adequate in vivo mammalian cell assay.  The Agency is not requesting any of these studies at this time and does not believe a UFDB is required for the lack of these studies.  Based on the proposed uses, quantification of risk is limited to short- and intermediate-term inhalation exposure for workers.  The PoD used for assessing repeated inhalation exposure is based on the most sensitive endpoint in the most sensitive species (dogs) and supported by the observation of similar effects at a comparable dose in the rat.  Consequently, the risk assessment does not underestimate potential risks to occupational workers and a total uncertainty factor of 100 is adequate.
 
  3.0	PROPOSED USE PATTERNS

Tolclofos-methyl is a new active ingredient being proposed for seed treatment use on various crops, turf grass, ornamental flower, and conifers.  The proposed formulated product is a liquid containing 42.0% tolclofos-methyl active ingredient (4.17 lbs tolclofos-methyl per gallon).  The proposed label is for both commercial and on-farm seed treatment.  The proposed label restricts the use of tolclofos-methyl in hopper-box or planter-box seed treatment systems at planting time.  The proposed label also states that the product is only to be applied to "true seeds" and is not to be applied on other propagation parts.  The application rates range from 0.000489 to 0.00000977 lb ai/lb seed.
 
Table 3.0:  Use Profile for Proposed Tolclofos-methyl Uses
                 Rizolex Flowable Fungicide (Reg. No. XXX-XXX)
                suspension concentrate (SC), 4.17 lb ai/gallon
                                     Crops
                             Application Equipment
                                    Maximum
                               Application Rate
                                     Notes
- Root and Tuber Vegetables (Crop Group 1A)
  Commercial Seed Treatment Facility and On-Farm Standard Slurry or Mist-Type
                            0.000489 lb ai/lb seed
except Burdock, Chervil, Turnip-Rooted; Ginseng; Horseradish; Salsify; Skirret;
- Cotton
                                       
                                       

- Bulb Vegetables (Crop Group 3-7)
  Commercial Seed Treatment Facility and On-Farm Standard Slurry or Mist-Type
                           0.00000977 lb ai/lb seed
except Daylily, Bulb; Elegans Hosta; Fritillaria, Bulb; Fritillaria, Leaves; Garlic, Bulb; Garlic, Great-Headed, Bulb; Garlic, Serpent, Bulb; Lily, Bulb; Onion, Chinese, Bulb; Onion, Macrostem; Onion, Tree, Tops; Onion, Welsh, Tops; Shallot, Bulb ; Shallot, Fresh Leaves
- Leafy Vegetables (Crop Group 4)
                                       
                                       
except Brassica Vegetables
- Brassica (Cole) Leafy Vegetables (Crop Group 5)
                                       
                                       

- Legume Vegetables (Succulent or Dried) (Crop Group 6)
                                       
                                       

- Fruiting Vegetables (Crop Group 8-10)
                                       
                                       

- Cucurbit Vegetables (Crop Group 9)
                                       
                                       

- Cereal Grains (Crop Group 15)
                                       
                                       
except Rice and Wildrice
- Grass Forage, Fodder, and Hay (Crop Group 17)
                                       
                                       

- Non-grass Animal Feeds (Forage, Fodder, Straw, and Hay) (Crop Group 18)
                                       
                                       

- Herbs and Spices (Crop Group 19)
                                       
                                       

- Oilseeds (Crop Group 20)
                                       
                                       
except cotton
- Ornamental Flowers
                                       
                                       

- Conifers
                                       
                                       

4.0	RESIDENTIAL (NON-OCCUPATIONAL) EXPOSURE
		
Residential exposure and risk estimates are not assessed in this document because the proposed uses of tolclofos-methyl do not involve applications by homeowners or commercial applicators in residential settings at this time and there are no existing or proposed residential uses.

5.0	OCCUPATIONAL EXPOSURE/RISK PATHWAY

Occupational handler exposure to tolclofos-methyl is expected for handlers involved in commercial seed treatment and on-farm seed treatment (not for direct use in a hopper-box or planter-box).  However, with respect to treated seed, exposure from post-application activities is unlikely.

5.1	Seed Treatment Occupational Handler

Occupational seed treatment handlers may experience short- and intermediate-term exposure to tolclofos-methyl while performing seed treatment activities in commercial settings.  In addition, occupational secondary handlers may experience short- and intermediate-term exposure while planting tolclofos-methyl -treated seeds.  No chemical-specific handler exposure data were submitted in support of this use pattern.  For assessing commercial seed treatment and seed planting activities, unit exposure data were taken from HED ExpoSAC Policy 14: SOPs for Seed Treatment.  The amount of active ingredient handled depends on the application rate (lb ai/lb seed), the pounds of seed treated in a day, and the pounds of seed that can be planted in a day, all of which vary depending upon the seed type.  Values for the amount of seed treated and planted per day were obtained from HED ExpoSAC Policy 14 and 15 as well as information obtained from the Biological and Economic Analysis Division (BEAD) memo entitled, "Acres Planted per Day and Seeding Rates of Crops Grown in the United States" (J. Becker and S. Ratnayake; 3/24/11).  

Treating Seed (Primary Handler)

Potential occupational exposure scenarios from the use of tolclofos-methyl as a commercial seed treatment include:
   * Mixing, loading, applying liquid formulations;
   * Bagging treated seed;
   * Sewing bags; and
   * Multiple activities.
   
Typically, for large-scale commercial seed treatments, workers perform only those specific individual tasks listed above; however, it is assumed that workers also may perform multiple activities throughout the day.  As a result a "multiple activities" scenario (i.e. where one worker performs all seed treatment tasks such as loading/applying, sewing, bagging, cleaning, calibration, repair, forklift driver, etc.) was addressed.

Planting Treated Seed (Secondary Handler)

Potential occupational exposure scenarios from the use of tolclofos-methyl as a commercial seed treatment include planting treated seed (secondary handler).

Planting treated seed consists of the farmer purchasing bags of treated seed, placing the seed in the hopper and applying seed to fields (considered a secondary handler exposure scenario).
5.3.1	Exposure Data, Factors, and Assumptions
 
The following are exposure factors and assumptions used to calculate exposure and risk estimates in the occupational assessment for commercial seed treatment scenarios.  

Unit Exposures 

Chemical-specific data for assessing exposure during commercial seed treatment and seed planting were not submitted to the Agency in support of this Section 3 application. Unit exposures are from ExpoSAC Policy 14: SOPs for Seed Treatment (May 1, 2003).  Unit exposure values from ExpoSAC Policy 14 are based on data for open mixing/loading/application systems. 

Amount of Seed Treated Per Day (Primary Handler)

HED is currently in the process of revising ExpoSAC Policy 15: Amount of Seed Treated or Planted per Day (March 2, 2004) in efforts to update the daily amount of seed treated in commercial seed treatment facilities.  With the increasing demand for hybridized treated seeds, there have been modifications not only in the seed treatment equipment, but in the market shares of new and currently registered pesticide products.  HED understands that due to the high cost of producing hybrid seeds, direct seeding is done in a precision manner which requires lower volumes of seed per acre.  However, this does not provide a direct correlation to the amount of seed which is treated in the commercial seed treatment facilities.   

The amount of seed treated per day at a commercial facility is summarized below for each crop.   
   * Root and Tuber Vegetables (Crop Group 1, except potato, sweet potato, and yam bean)- 5,500 lbs
   * Bulb Vegetables (Crop Group 3-01)- 5,500 lbs
   * Leafy Vegetables (except brassica vegetables) (Crop Group 4) - 5,500 lbs
   * Brassica (Cole) Leafy Vegetables (Crop Group 5) - 5,500 lbs
   * Legume Vegetables (Succulent or Dried) (Crop Group 6) - 5,500 lbs
   * Fruiting Vegetables (Crop Group 8-10) - 5,500 lbs
   * Cucurbit Vegetables (Crop Group 9) - 5,500 lbs
   * Cereal Grains (Crop Group 15, except rice and wildrice) - 718,000 lbs
   * Grass Forage, Fodder, and Hay (Crop Group 17) - 718,000 lbs
   * Non-grass Animal Feeds (Forage, Fodder, Straw, and Hay) (Crop Group 18) - 718,000 lbs
   * Herbs and Spices (Crop Group 19) - 5,500 lbs
   * Oilseeds (Crop Group 20, except Cotton) - 718,000 lbs
   * Cotton  -  160,000 lbs
   * Ornamental Flowers -  5,500 lbs
   * Conifers  -  2,000 lbs

Amount of Seed Planted Per Day (Secondary Handler)

Based on ExpoSAC Policy 15: Amount of Seed Treated or Planted per Day, the amount of seed planted per day is summarized below for each crop.  The amount of seed planted per day incorporates the information available from the BEAD memo entitled, "Acres Planted per Day and Seeding Rates of Crops Grown in the United States" (J. Becker and S. Ratnayake; 3/24/11).  The amount of seed planted per day for ornamental seeds was obtained by researching various ornamental and grower websites to obtain a seeding rate for the flower types identified by the registrant (i.e., zinnias, marigolds, lupine, dianthus, cyclamen, and verbenias).  Typical seeding rates for these types of flowers appear to range from less than 1 lb of seed per acre to 11 lbs of seed per acre.  To be protective of the various seed types, HED assumes that up to 11 lbs of ornamental flower seed can be planted per acre (or 440 lbs of seed planted per day).  

   * Root and Tuber Vegetables (Crop Group 1, except potato, sweet potato, and yam bean)- 2,614 lbs
   * Bulb Vegetables (Crop Group 3-01)- 1,004 lbs
   * Leafy Vegetables (except brassica vegetables) (Crop Group 4) - 697 lbs
   * Brassica (Cole) Leafy Vegetables (Crop Group 5) - 211 lbs
   * Legume Vegetables (Succulent or Dried) (Crop Group 6)  -  32,920 lbs
   * Fruiting Vegetables (Crop Group 8-10) - 209 lbs
   * Cucurbit Vegetables (Crop Group 9)  -  726 lbs
   * Cereal Grains (Crop Group 15, except rice and wildrice) - 37,500 lbs
   * Grass Forage, Fodder, and Hay (Crop Group 17)  -  2,800 lbs
   * Non-grass Animal Feeds (Forage, Fodder, Straw, and Hay) (Crop Group 18)  -  12,800 lbs
   * Herbs and Spices (Crop Group 19) - 836 lbs
   * Oilseeds (Crop Group 20, except Cotton) - 2,800 lbs
   * Cotton  -  2,667 lbs
   * Ornamental Flowers -  440 lbs
   * Conifers  -  2,000 lbs

Application Rates

The proposed treatment range is 0.00000977 to 0.000489 lb ai/lb seed for seed treatment.  The maximum application rates are shown above in Table 3. 

 Body Weight
 
The average adult weight of 80 kg was used for estimating inhalation exposure.  No dermal point of departure was selected, therefore a short- and intermediate-term dermal assessment is not being conducted for tolclofos-methyl.

Exposure Duration

It is anticipated that occupational tolclofos-methyl exposures will generally occur in short- (1-30 days) and intermediate- (1-6 months) term durations.

Absorption Factor

Since no inhalation absorption data are available, toxicity by the inhalation route is considered to be equivalent to the estimated toxicity by the oral route of exposure (100% absorption factor). 

Equations and Calculations
 
Daily Exposure
Daily handler exposures are estimated for each applicable handler task with the application rate, the amount of seed treated or seed planted in a day, and the applicable unit exposure using the following formula:

      Daily Exposure (mg ai/day)	=	Unit Exposure (mg ai/lb ai handled) * Application Rate (lbs ai/lb seed) * Daily Amount Handled (lbs seed/day)
      Where:  
          
          Daily Exposure	=	Amount (mg ai/day) deposited on the surface of the skin that is available for dermal absorption or amount inhaled that is available for inhalation absorption, 
          Unit Exposure	=	Unit exposure value (mg ai/day),
         Application Rate	=	Normalized application rate based on a logical unit treatment, such as pounds seed or acres; maximum values are used (lb ai/lb seed), and
         Daily Amount Handled	=	Amount seed treated per day (lb seed/day) or amount seed planted per day (lb seed/day).
 
Daily Dose
Daily dose (dermal or inhalation) was calculated by normalizing the daily dermal or inhalation exposure value by body weight and accounting for dermal and inhalation absorption. 
   
      Average Daily Dose (mg/kg/day) = Daily Exposure (mg ai/day) x {Absorption Factor (%/100)}
      						Body Weight (kg)
      Where:
         
         Average Daily Dose	=	Absorbed dose received from exposure to a pesticide in a given scenario (mg pesticide active ingredient/kg body weight/day),
         Daily Exposure	=	Amount (mg ai/day) deposited on the surface of the skin that is available for dermal absorption or amount inhaled that is available for inhalation absorption,
         Absorption Factor	=	A measure of the amount of chemical that crosses a biological boundary such as the lungs, and
         Body Weight	=	Body weight determined to represent the population of interest in a risk assessment.

Margin of Exposure (MOE)
The daily inhalation doses received by occupational handlers were compared to the appropriate points of departure (i.e. NOAELs) to assess the risk estimates to occupational handlers for each exposure route.  All MOEs were calculated using the following formula: 
	
      MOE    =	          NOAEL (mg/kg/day)
      		Average Daily Dose (mg/kg/day)
      Where:
         
         MOE	=	Margin of exposure value used by HED to represent risk or how close a chemical exposure is to being a concern (unitless),
         ADD	=	Average daily dose (ADD) is absorbed dose received from exposure to pesticide, and
         NOAEL	=	Dose level in a toxicity study, where no observed adverse effects occurred in the study.
5.3.2	Seed Treatment Handler Exposure and Risk Estimates Summary 	

Primary Handler

A summary of the inhalation risk estimates for each seed treatment exposure scenario is presented in Table 5 for short-term and intermediate-term inhalation exposures.  
      
The results of the occupational handler exposure and risk assessment indicate that inhalation risk estimates are not of concern (MOEs >= 100) at baseline attire (i.e., long-sleeved shirt, long pants, shoes and socks) and no respirator.  

HED is currently in the process of revising ExpoSAC Policy 15 in efforts to update the daily amount of seed treated in commercial seed treatment facilities.  With the increasing demand for hybridized treated seeds, there have been modifications not only in the seed treatment equipment, but in the market shares of new and currently registered pesticide products.  HED understands that due to the high cost of producing hybrid seeds, direct seeding is done in a precision manner which requires lower volumes of seed per acre.  However, this does not provide a direct correlation to the amount of seed which is treated in the commercial seed treatment facilities. Over the past several years, HED has received submissions from Industry for the use of several seed treatment pesticides which provide a range of daily amounts of vegetable seeds treated (1,000 to 5,500 lbs).  The amount chosen for many of the fruit, vegetable, and ornamental crop groups (5,500 lbs) is conservative.  For Crop Groups 15, 17, 18, and 20 the standard assumption of 718,000 lbs of seed treated is appropriate, as is the 160,000 lbs assumption for cotton.  

Based on an email submitted by Scott Enebak, director of the Forest Health Dynamics Laboratory at Auburn University, an average nursery produces 30,000,000 seedlings per year.  As such, 400-500 pounds of nursery tree seeds are treated per day for five days in the spring time during the treating season (enough to sow 30,000,000 seedlings).  Nursery tree seeds can range anywhere from 4,900 seeds/lb to 75,000 seeds/lb, with the majority of seeds falling in the range from 12,000 seeds/lb to 15,000 seeds/lb.  Table 4 shows the variation in the range of pine species seed sizes.  To be protective of the variations in seed size, HED assumes that up to 10,000,000 seeds can be treated per day (or 2,000 lbs, calculated from the most protective value of 4,900 seeds/lb). This value will be used to represent the treatment of conifer seeds. 

Table 4.	Amount of Seed Needed to Direct Seed an Acre and the Approximate Number of Seeds/Lb.
                                 Pine Species
                        Pounds of Seed Needed Per Acre
                     Approximate Number of Seeds Per Pound
                                   Loblolly
                                      0.5
                                    18,200
                                     Slash
                                      0.6
                                    13,500
                                   Longleaf
                                      2.5
                                     4,900
                                     Sand
                                      0.6
                                    75,000
a	Data from Forest Regeneration Methods: Natural Regeneration, Direct Seeding and Planting, M. L. Duryea, University of Florida Extension, Institute of Food and Agricultural Sciences, Circular 759, March 1992.

Secondary Handler

Table 6 shows that the planter (secondary handler) short- and intermediate-term inhalation exposure risk estimates result in MOEs ranging from 160,000 to 24,000,000.  These risk estimates do not exceed HED's level of concern (MOE  >= 100) at some level of risk mitigation (i.e., gloves, no respirator) for handlers planting treated seed.

Nursery tree seedling planting is predominantly mechanized, and thus secondary handler exposure to planting treated nursery seeds is expected to be very low.  Pine seeds are planted with seed drills that are capable of drilling several million seeds per day, averaging 6,000,000 seeds per day for medium sized nurseries of average production, equating to an average of 10 acres of seed sown per day (e-mail correspondence with Scott Enebak, Director of Forest Health Dynamics Laboratory, Auburn University).  To be protective of the variations in seed size, HED assumes that up to 10,000,000 seeds can be planted per day in a larger nursery (or 2,000 lbs, calculated from the most protective value of 4,900 seeds/lb). This assumption was determined to be appropriate for conifer seeds as well. 

On-Farm Seed Treatment

On-farm seed treatment utilizes similar machinery as commercial seed treatment; the only difference being the size of the equipment.  With the specific label restricting direct product use in hopper-boxes and planter-boxes, the assessed commercial seed treatment exposure and risk estimates are protective of on-farm seed treatment scenarios.

5.4	Seed Treatment Occupational Post-Application Exposures and Risk Estimates 	 

A post-application inhalation exposure assessment is not required as exposure is expected to be negligible.  Seed treatment assessments provide quantitative inhalation exposure assessments for seed treaters and secondary handlers (i.e.planters).  It is expected that these exposure estimates would be protective of most post-application inhalation exposure scenarios.

The potential for post-application exposures following the planting of tolclofos-methyl-treated seeds is unlikely.  Sustained levels of contact with treated seed after it has been placed in the soil or other planting media would not be expected because no routine cultural practice required for the production of agricultural commodities involves such an activity as defined in the no/low contact criteria in the Worker Protection Standard (WPS).  As a result, no quantitative post-application assessment is required for exposure to treated seeds that have already been planted.

The labeling should state:  Seed that has been treated with this product that is then packaged or bagged for future use must contain the following labeling on the outside of the seed package or bag. 
      "Treated Seed - Do Not Use for Food, Feed, or Oil Purposes. Store away from feeds and other foodstuffs.  
      When opening this bag or loading/pouring the treated seed, wear a long-sleeved shirt, long pants, shoes, socks, and chemical resistant gloves.  After the seeds have been planted, do not enter or allow worker entry into treated areas during the restricted-entry interval (REI) of 12 hours. Exception: Once the seeds are planted in soil or other planting media, the Worker Protection Standard allows workers to enter the treated area without restriction if there will be no worker contact with the treated seeds in the soil or planting media."

Table 5.	Summary of Short- and Intermediate-Term Handler Exposures and Risk Estimates for Tolclofos-methyl 
                                   Seed Type
                                  Inhal UE[a]
                                Max App Rate[b]
                                Amt Treated[c]
                                 Inhal Dose[d]
                                 Inhal MOE[e]
                                       
                                     mg/lb
                                 lb ai/lb seed
                                  lb seed/day
                                   mg/kg/day
                                   LOC = 100
                   LOADER/APPLICATOR (single layer, gloves)
Root and Tuber Vegetables (Crop Group 1, except potato, sweet potato, and yam bean)
                                    0.00034
                                   0.000489
                                     5,500
                                   1.14E-05
                                   2,000,000
                       Bulb Vegetables (Crop Group 3-01)
                                    0.00034
                                  0.00009773
                                     5,500
                                   2.28E-06
                                  10,000,000
         Leafy Vegetables (except brassica vegetables) (Crop Group 4)
                                    0.00034
                                  0.00009773
                                     5,500
                                   2.28E-06
                                  10,000,000
                Brassica (Cole) Leafy Vegetables (Crop Group 5)
                                    0.00034
                                  0.00009773
                                     5,500
                                   2.28E-06
                                  10,000,000
             Legume Vegetables (Succulent or Dried) (Crop Group 6)
                                    0.00034
                                  0.00009773
                                     5,500
                                   2.28E-06
                                  10,000,000
                     Fruiting Vegetables (Crop Group 8-10)
                                    0.00034
                                  0.00009773
                                     5,500
                                   2.28E-06
                                  10,000,000
                      Cucurbit Vegetables (Crop Group 9)
                                    0.00034
                                  0.00009773
                                     5,500
                                   2.28E-06
                                  10,000,000
            Cereal Grains (Crop Group 15, except rice and wildrice)
                                    0.00034
                                  0.00009773
                                    718,000
                                   2.98E-04
                                    77,000
                 Grass Forage, Fodder, and Hay (Crop Group 17)
                                    0.00034
                                  0.00009773
                                    718,000
                                   2.98E-04
                                    77,000
    Non-grass Animal Feeds (Forage, Fodder, Straw, and Hay) (Crop Group 18)
                                    0.00034
                                  0.00009773
                                    718,000
                                   2.98E-04
                                    77,000
                       Herbs and Spices (Crop Group 19)
                                    0.00034
                                  0.00009773
                                     5,500
                                   2.28E-06
                                  10,000,000
                    Oilseeds (Crop Group 20, except Cotton)
                                    0.00034
                                  0.00009773
                                    718,000
                                   2.98E-04
                                    77,000
                                    Cotton
                                    0.00034
                                   0.000489
                                    160,000
                                   3.33E-04
                                    69,000
                              Ornamental Flowers
                                    0.00034
                                  0.00009773
                                     5,500
                                   6.65E-05
                                    350,000
                                   Conifers
                                    0.00034
                                  0.00009773
                                     2,000
                                   8.31E-07
                                  28,000,000
                        SEWER (single layer, NO gloves)
Root and Tuber Vegetables (Crop Group 1, except potato, sweet potato, and yam bean)
                                    0.00023
                                   0.000489
                                     5,500
                                   7.73E-06
                                   3,000,000
                       Bulb Vegetables (Crop Group 3-01)
                                    0.00023
                                  0.00009773
                                     5,500
                                   1.55E-06
                                  15,000,000
         Leafy Vegetables (except brassica vegetables) (Crop Group 4)
                                    0.00023
                                  0.00009773
                                     5,500
                                   1.55E-06
                                  15,000,000
                Brassica (Cole) Leafy Vegetables (Crop Group 5)
                                    0.00023
                                  0.00009773
                                     5,500
                                   1.55E-06
                                  15,000,000
             Legume Vegetables (Succulent or Dried) (Crop Group 6)
                                    0.00023
                                  0.00009773
                                     5,500
                                   1.55E-06
                                  15,000,000
                     Fruiting Vegetables (Crop Group 8-10)
                                    0.00023
                                  0.00009773
                                     5,500
                                   1.55E-06
                                  15,000,000
                      Cucurbit Vegetables (Crop Group 9)
                                    0.00023
                                  0.00009773
                                     5,500
                                   1.55E-06
                                  15,000,000
            Cereal Grains (Crop Group 15, except rice and wildrice)
                                    0.00023
                                  0.00009773
                                    718,000
                                   2.02E-04
                                    110,000
                 Grass Forage, Fodder, and Hay (Crop Group 17)
                                    0.00023
                                  0.00009773
                                    718,000
                                   2.02E-04
                                    110,000
    Non-grass Animal Feeds (Forage, Fodder, Straw, and Hay) (Crop Group 18)
                                    0.00023
                                  0.00009773
                                    718,000
                                   2.02E-04
                                    110,000
                       Herbs and Spices (Crop Group 19)
                                    0.00023
                                  0.00009773
                                     5,500
                                   1.55E-06
                                  15,000,000
                    Oilseeds (Crop Group 20, except Cotton)
                                    0.00023
                                  0.00009773
                                    718,000
                                   2.02E-04
                                    110,000
                                    Cotton
                                    0.00023
                                   0.000489
                                    160,000
                                   2.25E-04
                                    100,000
                              Ornamental Flowers
                                    0.00023
                                  0.00009773
                                     5,500
                                   4.50E-05
                                    510,000
                                   Conifers
                                    0.00023
                                  0.00009773
                                     2,000
                                   5.62E-07
                                  41,000,000
                       BAGGER (single layer, NO gloves)
Root and Tuber Vegetables (Crop Group 1, except potato, sweet potato, and yam bean)
                                    0.00016
                                   0.000489
                                     5,500
                                   5.38E-06
                                   4,300,000
                       Bulb Vegetables (Crop Group 3-01)
                                    0.00016
                                  0.00009773
                                     5,500
                                   1.08E-06
                                  21,000,000
         Leafy Vegetables (except brassica vegetables) (Crop Group 4)
                                    0.00016
                                  0.00009773
                                     5,500
                                   1.08E-06
                                  21,000,000
                Brassica (Cole) Leafy Vegetables (Crop Group 5)
                                    0.00016
                                  0.00009773
                                     5,500
                                   1.08E-06
                                  21,000,000
             Legume Vegetables (Succulent or Dried) (Crop Group 6)
                                    0.00016
                                  0.00009773
                                     5,500
                                   1.08E-06
                                  21,000,000
                     Fruiting Vegetables (Crop Group 8-10)
                                    0.00016
                                  0.00009773
                                     5,500
                                   1.08E-06
                                  21,000,000
                      Cucurbit Vegetables (Crop Group 9)
                                    0.00016
                                  0.00009773
                                     5,500
                                   1.08E-06
                                  21,000,000
            Cereal Grains (Crop Group 15, except rice and wildrice)
                                    0.00016
                                  0.00009773
                                    718,000
                                   1.40E-04
                                    160,000
                 Grass Forage, Fodder, and Hay (Crop Group 17)
                                    0.00016
                                  0.00009773
                                    718,000
                                   1.40E-04
                                    160,000
    Non-grass Animal Feeds (Forage, Fodder, Straw, and Hay) (Crop Group 18)
                                    0.00016
                                  0.00009773
                                    718,000
                                   1.40E-04
                                    160,000
                       Herbs and Spices (Crop Group 19)
                                    0.00016
                                  0.00009773
                                     5,500
                                   1.08E-06
                                  21,000,000
                    Oilseeds (Crop Group 20, except Cotton)
                                    0.00016
                                  0.00009773
                                    718,000
                                   1.40E-04
                                    160,000
                                    Cotton
                                    0.00016
                                   0.000489
                                    160,000
                                   1.56E-04
                                    150,000
                              Ornamental Flowers
                                    0.00016
                                  0.00009773
                                     5,500
                                   3.13E-05
                                    740,000
                                   Conifers
                                    0.00016
                                  0.00009773
                                     2,000
                                   3.91E-07
                                  59,000,000
MULTIPLE ACTIVITIES (combination of loader/applicator with gloves + no coveralls, sewer without gloves, stacker without gloves)
Root and Tuber Vegetables (Crop Group 1, except potato, sweet potato, and yam bean)
                                    0.0016
                                   0.000489
                                     5,500
                                   5.38E-05
                                    430,000
                       Bulb Vegetables (Crop Group 3-01)
                                    0.0016
                                  0.00009773
                                     5,500
                                   1.08E-05
                                   2,100,000
         Leafy Vegetables (except brassica vegetables) (Crop Group 4)
                                    0.0016
                                  0.00009773
                                     5,500
                                   1.08E-05
                                   2,100,000
                Brassica (Cole) Leafy Vegetables (Crop Group 5)
                                    0.0016
                                  0.00009773
                                     5,500
                                   1.08E-05
                                   2,100,000
             Legume Vegetables (Succulent or Dried) (Crop Group 6)
                                    0.0016
                                  0.00009773
                                     5,500
                                   1.08E-05
                                   2,100,000
                     Fruiting Vegetables (Crop Group 8-10)
                                    0.0016
                                  0.00009773
                                     5,500
                                   1.08E-05
                                   2,100,000
                      Cucurbit Vegetables (Crop Group 9)
                                    0.0016
                                  0.00009773
                                     5,500
                                   1.08E-05
                                   2,100,000
            Cereal Grains (Crop Group 15, except rice and wildrice)
                                    0.0016
                                  0.00009773
                                    718,000
                                   1.40E-03
                                    16,000
                 Grass Forage, Fodder, and Hay (Crop Group 17)
                                    0.0016
                                  0.00009773
                                    718,000
                                   1.40E-03
                                    16,000
    Non-grass Animal Feeds (Forage, Fodder, Straw, and Hay) (Crop Group 18)
                                    0.0016
                                  0.00009773
                                    718,000
                                   1.40E-03
                                    16,000
                       Herbs and Spices (Crop Group 19)
                                    0.0016
                                  0.00009773
                                     5,500
                                   1.08E-05
                                   2,100,000
                    Oilseeds (Crop Group 20, except Cotton)
                                    0.0016
                                  0.00009773
                                    718,000
                                   1.40E-03
                                    16,000
                                    Cotton
                                    0.0016
                                   0.000489
                                    160,000
                                   1.56E-03
                                    15,000
                              Ornamental Flowers
                                    0.0016
                                  0.00009773
                                     5,500
                                   3.13E-04
                                    74,000
                                   Conifers
                                    0.0016
                                  0.00009773
                                     2,000
                                   3.91E-06
                                   5,900,000
a	Unit Exposures from HED Exposure Science Advisory Council Policy 14 (baseline inhalation = no respirator).
b	Application Rates based on proposed label uses for tolclofos-methyl.
c	HED default for lb seed treated per day from HED Exposure Science Advisory Council Policy 15.
d	Daily Inhalation Dose (mg/kg/day) = daily inhalation unit exposure (mg/ - lb ai) x application rate (lb ai/lb seed) x amount treated (lb seed/day) x absorption factor (100%) / -  body weight (80 kg adult).
e	Inhalation MOE = NOAEL (23.0 mg/kg/day for short- and intermediate-term exposure) / Inhalation Dose (mg/kg/day). Level of concern = 100.
      
Table 6.	Summary of Secondary Handler (Planter) Exposures and Risk Estimates for Tolclofos-methyl (Single Layer, Gloves for Loading Only).
                                   Seed Type
                                Represented by
                            Max lbs of seed/acre[a]
                                  Inhal UE[b]
                                Max App Rate[c]
                          Amt of Seed Planted/Day[d]
                              Inhalation Dose[e]
                               Inhalation MOE[f]
                                       
                                       
                                 lb seed/acre
                                     mg/lb
                                 lb ai/lb seed
                                  lb seed/day
                                   mg/kg/day
                                   LOC = 100
Root and Tuber Vegetables (Crop Group 1, except potato, sweet potato, and yam bean)
                                    radish
                                      33
                                      3.4
                                   0.000489
                                     2,614
                                   5.43E-05
                                    420,000
                       Bulb Vegetables (Crop Group 3-01)
                                  onion seed
                                      13
                                      3.4
                                  0.00009773
                                     1,004
                                   4.17E-06
                                   5,500,000
         Leafy Vegetables (except brassica vegetables) (Crop Group 4)
                                    spinach
                                       9
                                      3.4
                                  0.00009773
                                      697
                                   2.89E-06
                                   8,000,000
                Brassica (Cole) Leafy Vegetables (Crop Group 5)
                                   broccoli
                                       3
                                      3.4
                                  0.00009773
                                      211
                                   8.76E-07
                                   26,000,00
             Legume Vegetables (Succulent or Dried) (Crop Group 6)
                                  pea, garden
                                      412
                                      3.4
                                  0.00009773
                                    32,920
                                   1.37E-04
                                    170,000
                     Fruiting Vegetables (Crop Group 8-10)
                                  bell pepper
                                       3
                                      3.4
                                  0.00009773
                                      209
                                   8.68E-07
                                  26,000,000
                      Cucurbit Vegetables (Crop Group 9)
                                  watermelon
                                       9
                                      3.4
                                  0.00009773
                                      726
                                   3.02E-06
                                   7,600,000
            Cereal Grains (Crop Group 15, except rice and wildrice)
                                wheat (table 7)
                                      188
                                      3.4
                                  0.00009773
                                    37,500
                                   1.56E-04
                                    150,000
                 Grass Forage, Fodder, and Hay (Crop Group 17)
                              bluegrass, kentucky
                                      35
                                      3.4
                                  0.00009773
                                     2,800
                                   1.16E-05
                                   2,000,000
    Non-grass Animal Feeds (Forage, Fodder, Straw, and Hay) (Crop Group 18)
                                     lupin
                                      160
                                      3.4
                                  0.00009773
                                    12,800
                                   5.32E-05
                                    430,000
                       Herbs and Spices (Crop Group 19)
                                    parsely
                                      10
                                      3.4
                                  0.00009773
                                      836
                                   3.47E-06
                                   6,600,000
                    Oilseeds (Crop Group 20, except Cotton)
                                   safflower
                                      35
                                      3.4
                                  0.00009773
                                     2,800
                                   1.16E-05
                                   2,000,000
                                    Cotton
                                    cotton
                                      13
                                      3.4
                                   0.000489
                                     2,667
                                   5.54E-05
                                    420,000
                              Ornamental Flowers
                                flowers- varied
                                      11
                                      3.4
                                  0.00009773
                                      440
                                   1.83E-06
                                  12,600,000
                                   Conifers
                                     dust
                                      10
                                      3.4
                                  0.00009773
                                     2,000
                                   8.31E-06
                                   2,770,000
a	Information from  "Acres Planted per Day and Seeding Rates of Crops Grown in the United States" (J. Becker and S. Ratnayake; 3/24/11).: Number of seeds per acre (Table 10) / Number of seeds per lb (Table B-1) = Max lbs of seed per acre
b	Unit Exposures from HED Exposure Science Advisory Council Policy 14: Standard Operating Procedures for Seed Treatment  (baseline inhalation = no respirator).
c	Application Rates based on proposed label uses for tolclofos-methyl.
d	Incorporation of acres treated per day from HED Exposure Science Advisory Council Policy 15 and "Acres Planted per Day and Seeding Rates of Crops Grown in the United States" (J. Becker and S. Ratnayake; 3/24/11): Max lbs of seed per acre x acres planted per day (Policy 15 Table 3)
e	Daily Inhalation Dose (mg/kg/day) = daily inhalation unit exposure (mg/ - lb ai) x application rate (lb ai/lb seed) x amount planted (lb seed/day) x absorption factor (100%) / -  body weight (80 kg adult).
f	Inhalation MOE = NOAEL (23 mg/kg/day for short- and intermediate-term exposure) / Inhalation Dose (mg/kg/day). Level of concern = 100.