OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION 

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



## VIA E

- MAIL

July 1 8 , 201 3

Rebecca A. Clemmer United Phosphorus, Inc. 630 Freedom Business Center, Suite 402 King of Prussia, PA 19406

Subject: Sodium Asulam Registration Review Data Call

- in

Dear Ms. Clemmer :

As part of United Phosphorus’ (UniPhos) 90

- day response to the generic data call

- in ( G DC I) notice

GDCI

- 106902

- 1013, it requested a waiver fr om the neurotoxicity battery ( GLN 870.6200) data requirement

. On February 21, 2013, the Health Effects Division’s (HED) Hazard and Science Policy Council ( HASPOC ) review ed the subject waiver request, and also considered the entire

asulam toxicology data base, and specifically subchronic dermal toxicity, developmental thyroid toxicity

, and subchronic inhalation toxicity which were studies required through a previous GDCI (GD CI

- 106902

- 21930 ). This letter summarizes conclusions reached by the Office of Pesticide Programs on data requirements for asulam.

Regarding the waiver request by UniPhos for the neurotoxicity battery ( GLN 870.6200) , levied via

GDCI

- 106902

- 1013, the Age ncy has determined that based upon (i) the lack of neurotoxicity

exhibited in the available toxicity studies; (ii) the lack of neurotoxicity exhibited by chemicals similar to asulam; and (iii) the fact that the target organ for asulam is the thyroid, not t he nervous

system, an acute and sub

- chronic neurotoxicity study is not needed at this time.

Regarding the need f or developmental thyroid and subchronic dermal data

, the Agency previously

believed that these data would not inform the risk assessment cond ucted to support asulam’s Tolerance Reassessment Eligibility Decision (TRED) (J. Morales, D276505, 02/28/2002)

, because

there were sufficient margins of exposure (MOE)

. Yet, the Agency retained a 10X FQPA Safety

Factor , in the absence of these data

. Sinc e that time, the Agency has re

- examined potential risks from occupational exposure (as noted in the Scoping Document for the registration review of asulam) , and may revise the residential risk assessment for asulam based on updated residential

exposure ass essment SOP’s. The Agency has revisited these data gaps i n light of the updated

## occupational exposure assessment and in consideration of the possible revision of the residential risk

assessment

.

B ecause the thyroid gland is the target organ for asulam , and there is potential toxicity to young based on thyroid toxicity observed in adult animals, the Agency believes that a non

- guideline developmental thyroid study may address potential age

- related sensitivity. Consequently, the Agency considers a develop mental thyroid study important to the human health risk assessment for

asulam. In conducting this study, it is recommended that a protocol with the dose selection be

submitted to the Agency for review prior to the initiation of this study. As before, the Agency will

retain a n additional 10X database uncertainty factor in the absence of these data.

Regarding subchronic dermal data (GLN 870.3200) , the Agency believes that these data are also important to the human health risk assessment for asulam based up on (i) the current range of occupational risk estimates ( MOEs range from 77

– 5,400 (with gloves), and an LOC of 10 0 0 ); (ii) identification of the thyroid as the target organ; and, (iii) the absence of accurate dermal absorption

data

. The current range of occupational MOEs is based on the use of an oral Point of Departure (POD) of 50 mg/kg day and a 30 % extrapolated dermal absorption factor (see enclosure , Table 1)

. Based upon this, t he registrant is asked to consider the following options: 1) conduct the 21 day dermal toxicity study to ascertain target organ toxicity following repeated dermal exposure or 2) perform an in vivo dermal penetration study (GLN 870.7600) t o refine the dermal absorption factor that is currently being used for dermal risk assessme nt. If the registrant elects to conduct the dermal toxicity study, then this study should include evaluation of thyroid hormones

, thyroid weight

, and thyroid histopathology

. In the absence of additional data on dermal toxicity or dermal absorption of

asul am will result in unacceptable MOEs and may force the Agency to require risk mitigation measures for asulam products.

With regard to subchronic inhalation data (GLN 870.3465)

, the Agency does not believe that these

data are needed at this time

.

Therefo re the Agency concludes th e following studies would inform the asulam hazard database for

the registration review of this compound.

o a developmental thyroid test (non

- guideline) and

,

o either a subchronic dermal study (GLN 870.3200), or a dermal penetration study (GLN 870.7600).

The following requirement is not needed at this time and, therefore, a data waiver is granted for :

o the neurotoxicity battery (GLN 870.6200)

.

Within 30 days of receiving this letter, please inform the Agency as to how UniPhos plans to address the data g aps identified in this letter.

For further discussion of these conclusions, please see the enclosed document, Asulam: Summary of Hazard and Science Policy coun cil (HASPOC) Meeting on January 17, 2013: Recommendations on data requirements for acute and subchronic neurotoxicity studies and immunotoxicity study and re

evaluation of previously waived studies . If you have any questions, or would like to speak furth er

## Table 1. Short

- Term Occupational Handler Exposure and Risk Estimates for Asulam with Varying Levels of Dermal PPE and No Respirator.

Exposure Scenario Crop or Target Dermal Unit Exposure (ug/lb ai) 1 Inhalation Unit Exposure

(ug/lb ai) 1

(No Respirator) Maximum
Application Rate

(lb ai/A or

gallon) 2 Area Treated Daily
(A or gal/

day) 2 Dermal Inhalation

Dose (mg/kg/day) 3 MOE 4 Dose (mg/kg/day) 5 MOE 6

Mixer/Loader

Mixing/Loading Liquid

Formulation for Aerial Application Sod

220 (baseline)

36.7 (gloves) 0.219 3.33

(lb ai/A) 350 A 1.1 0.19 (gloves) 45 260 (gloves) 0.0037 14,000

Sugarcane 1200 A 3.8 0.65 (gloves) 13 77 (gloves) 0.013 3,900

Mixing/Loading Liquid

Formulation for Groundboom Application Ornamentals 40 A 0.13 0.022 (gloves) 390 2,300 (gloves) 0.00042 120,000

Sod 80 A 0.2 6 0.044 (gloves) 200 1,100 (gloves) 0.00085 59,000

Sugarcane 200 A 0.64 0.11 (gloves) 78 460 (gloves) 0.0021 24,000

Applicator

Applying Liquids as an Aerial Spray Sod 5
(engineering

control) 0.068

3.33

(lb ai/A) 350 A 0.025 2,000 0.0012 43,000

Sugarcane 1200 A 0.087 570 0.0039 13,000

Applying Liquids with a

Groundboom Sprayer Ornamentals

78.6 (baseline)
16.1 (gloves) 0.34 40 A 0.046 0.0093 (gloves) 1,100 5,400 (gloves) 0.00066 76,000

Sod 80 A 0.091 0.019 (gloves) 550 2700 (gloves) 0.0013 38,000

Sugarcane 200 A 0.23 0.047 (gloves) 220 1,100 (gloves) 0.0033 15,000

Applying Liquids with a Mechanically

- pressurized Handgun Rights

- of

- way 1,300 (baseline)
390 (gloves) 3.9 0.208
(lb ai/gal) 1,000
gallons 1.2 0.35 (gloves) 43 140 (gloves) 0.012 4,200

## Table 1. Short

- Term Occupational Handler Exposure and Risk Estimates for Asulam with Varying Levels of Dermal PPE and No Respirator.

Exposure Scenario Crop or Target Dermal Unit Exposure (ug/lb ai) 1 Inhalation Unit Exposure

(ug/lb ai) 1

(No Respirator) Maximum
Application Rate

(lb ai/A or

gallon) 2 Area Treated Daily
(A or gal/

day) 2 Dermal Inhalation

Dose (mg/kg/day) 3 MOE 4 Dose (mg/kg/day) 5 MOE 6

Flagger

Flagging for Aerial Applications Sod & Sugarcane 11 (baseline)
12 (gloves) 0.35 3.33

(lb ai/A) 350 A 0.05 6
0.061 (gloves) 900
820 (gloves) 0.0059 8,500

Mixer/Loader/Applicator

Mixing/Loading/Applying with a Backpack Sprayer Rights

- of

- way 8260 (baseline)
8260 (gloves) 2.58

0.208
(lb ai/gal) 40
gallons 0.30 0.30 (gloves) 170 170 (gloves) 0.00031 160,000

Christmas Tree

farm 13,200 (baseline)
11,200 (gloves) 140 40
gallons 0.48 0.41 (gloves) 100 120 (gloves) 0.017 3,000

Mixing/Loading/Applying with a Manually

pressurized Handwand Christmas Tree

farm 100,000 (baseline)
430 (gloves) 30 40
gallons 3.6 0.016 (gloves) 14 3,200 (gloves) 0.0036 14,000

Mixing/Loading/Applying

with a Mechanically

pressurized Handgun 1,300 (baseline)
390 (gloves) 3.9 1,000
gallons 1.2 0.35 (gloves) 43 140 (gloves) 0.012 4,200

1 Based on “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table”; includes data from PHED/ORETF /AHETF (Dermal “ Baseline ” indicates no gloves or coveralls; all inhalation values reflect no respirator ).

2 Based on maximum label application rate.

3 Dermal Dose = Dermal Unit Exposure (ug/lb ai) x Conversion Factor (0.001 mg/ug) x Dermal Absorption (30%) x Application Rate (lb ai/ A or gal ) x Area Treated Daily ( A or gal /day) /BW ( 69 kg).

4 Dermal MOE = Dermal NOAEL ( 50 mg/kg/day)/Dermal Dose (mg/kg/day).

5 Inhalation Dose = Dermal Unit Exposure (ug/lb ai) x Conversion Factor (0.001 mg/ug) x Application Rate (lb ai/ A or gal ) x Area Treated Daily ( A or gal /day) /BW ( 69 kg).

6 Inhalation MOE = Inhalation NOAEL ( 50 mg/kg/day)/ Inhalation Dose (mg/kg/day).

## T able 2. Occupational Post

- application Exposure and Risk Estimates for Asulam

.

Crop/Site Activities Transfer Coefficient (cm 2 /hr) DAT 1 DFR/TTR 2
(μg/cm 2 ) Dermal Dose (mg/kg/day) 3 MOE 4

Short

- term

Ornamentals Pruning, Weeding, Container moving, Hand harvesting 230 0 9.34 0.075 670

1 8.41 0.067 740

2 7.57 0.061 830

3 6.81 0.055 920

4 6.13 0.049 1000

Sod Maintenance, Harvesting, Transplanting 6,700 0 0.374 0.087 570

1 0.336 0.078 640

2 0.303 0.071 710

6 0.199 0.046 1100

Sugarcane Scouting 1,100 0 9.34 0.357 140

1 8.41 0.322 160

2 7.57 0.29 170

18 1.4 0.0536 930

19 1.26 0.0482 1000

1 DAT = Day after treatment for which residues, doses and MOEs are estimated.

2 DFR = Application Rate 

### × F 

### × (1

- D) t 

### × 4.54E8 μg/lb 

### × 2.47E

- 8 acre/cm 2 ; where F = 0.25 and D = 0.10 per day ; TTR = Application Rate 

### × F 

### × (1

- D) t 

### × 4.54E8 μg/lb 

### × 2.47E

- 8

acre/cm 2 ; where F = 0.1 and D = 0.10 per day

3 Daily Dermal Dose = [DFR /TTR (μg/cm 2 ) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption ( 30 %)] ÷ BW ( 69 kg).

4 MOE = POD ( 50 mg/kg/day) / Daily Dermal Dose.