OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

VIA E-MAIL

July 18, 2013

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 (GDCI) notice 

GDCI-106902-1013, it requested a waiver from the neurotoxicity battery (GLN 870.6200) data 

requirement. On February 21, 2013, the Health Effects Division’s (HED) Hazard and Science 

Policy Council (HASPOC) reviewed 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 

(GDCI-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 Agency 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 the nervous 

system, an acute and sub-chronic neurotoxicity study is not needed at this time. 

Regarding the need for developmental thyroid and subchronic dermal data, the Agency previously 

believed that these data would not inform the risk assessment conducted 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. Since 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 assessment SOP’s. The Agency has revisited these data gaps in light of the updated 
occupational exposure assessment and in consideration of the possible revision of the residential risk 

assessment. 

Because 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 developmental 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 an 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 upon (i) the current range of 

occupational risk estimates (MOEs range from 77 – 5,400 (with gloves), and an LOC of 1000); (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, the 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) to refine the dermal absorption factor 

that is currently being used for dermal risk assessment. 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 

asulam 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.

Therefore the Agency concludes the 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 gaps identified in this letter. 

For further discussion of these conclusions, please see the enclosed document, Asulam: Summary of 

Hazard and Science Policy council (HASPOC) Meeting on January 17, 2013: Recommendations on 

data requirements for acute and subchronic neurotoxicity studies and immunotoxicity study and reevaluation of previously waived studies. If you have any questions, or would like to speak further 

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 MOE4 Dose (mg/kg/day)5 MOE6

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 0.26

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 MOE4 Dose (mg/kg/day)5 MOE6

Flagger

Flagging for Aerial 

Applications

Sod & 

Sugarcane

11 (baseline)

12 (gloves) 0.35 3.33(lb ai/A) 350 A 0.0560.061 (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 40gallons

0.48

0.41 (gloves)

100

120 (gloves) 0.017 3,000

Mixing/Loading/Applying 

with a Manuallypressurized Handwand Christmas Tree 

farm

100,000 (baseline)

430 (gloves) 30 40gallons

3.6

0.016 (gloves)

14

3,200 (gloves) 0.0036 14,000

Mixing/Loading/Applying 

with a Mechanicallypressurized Handgun

1,300 (baseline)

390 (gloves) 3.9 1,000gallons

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).
Table 2. Occupational Post-application Exposure and Risk Estimates for Asulam.

Crop/Site Activities Transfer Coefficient 

(cm2/hr) DAT1 DFR/TTR2(μg/cm2)

Dermal Dose 

(mg/kg/day)3 MOE4

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/cm2

; 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/cm2

; where F = 0.1 and D = 0.10 per day 

3 Daily Dermal Dose = [DFR/TTR (μg/cm2

) × 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.