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EFED Guideline Comments, Registrant Comments, and EFED response to 

Registrant Comments

835.4400 Anaerobic aquatic metabolism: 

A study has been submitted that is scientifically valid but additional characterization of secondary 

metabolites is anticipated to be required.

DuPont Comments: DuPont believes that further characterization of secondary metabolites should not 

be warranted based on OPPTS guideline 835.4400 and the facts below:

1. The overall mass balance was 101.1±3.9% (the data summarized from Table VI, VII, and VIII in MRID 

#48332004).

2. All major metabolites (IN-70942, IN-70941, IN-J0290, and IN-E9260) were well identified by HPLC 

method and confirmed by the secondary TLC method, which is consistent with other rimsulfuron aerobic 

and anaerobic degradation studies. 3. Unknown 1 from the combined amount of sediment and water 

phases (as shown in Tables IX, X, XIII, and XIV in MRID #48332004) was indicated greater than 10%. 

However, Unknown 1 was not a single metabolite; rather it was the sum of multiple polar components not 

retained by original HPLC method. Unknown 1 was separated into 4 distinct approximately equal peaks 

by modified HPLC as demonstrated in Figure 17 from MRID #48332004. Therefore, no single component 

was indicated greater than 10% or even 5%.

EFED Response to Comment:

EFED has reviewed the information cited in DuPont’s response and agrees in principle with each 

of the points made. However, DuPont did not in their response discuss the identity of unextracted 

residues or the possibility of attempting further extraction steps to release these residues. The 

level of unextracted residues is high – for example, in Table VI on page 42 it is shown that the 

unextracted residues in nonsterile Canadian pond water and sediment at 25 C increased steadily 

over time (e.g., about 19% at 14 days and 71% of the applied radioactivity at 3 months after 

application). EFED reviewed the submitted report (MRID 48332004) and notes while the 

fraction of bound residues observed under nonsterile conditions is quite high, the registrant did 

extract the sediment three times with 2:1 acetonitrile:water and then three times with a methanol 

phosphate buffer system before declaring the remaining radioactivity as unextractable. Some 

characterization of the large amount of radiolabeled residues in the sediment was conducted by 

fractionation into humin, fulvic acid, and humic acid fractions The fractionation procedure 

needs to be described in more detail as only a citation of a Federal Register notice is given as a 

reference. 

Normally, the high degree of unextracted residues observed in the anaerobic aquatic metabolism 

study would be a basis for requesting an additional study, or, at the very least, necessitate more 

conservative assumptions in risk assessments (e.g., assuming that the the unextracted residues 

were part of the total toxic residues.) Somewhat reducing these concerns is that much of the 

formation and decline of parent to and from residues such as IN-70941, IN-70942, IN-J0290, and 

IN-E9260 occurs prior to most of the rise in the amount of unextracted radiolabeled residues.

Therefore most of the residues which become bound to soil organic matter or colloids would 

more likely be secondary metabolites of less toxicological concern. A special sediment toxicity 

study could further address whether any of the unextracted residues are of toxicological concern

and, if it were to show these residues to be non-toxic, might allow less conservative exposure 

assumptions to be made in future risk assessments.
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It is also relevant to note that unextracted residues while generally less than 25% in the aerobic 

soil metabolism studies, did appear to be rising when these studies were terminated after about 

four months incubation (MRID 48332003; study under review).

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835.6100 Terrestrial field dissipation study: 

State of the art Environmental Chemistry Method (ECM) for trace residues in soil and Independent 

Laboratory Validation (ILV) is requested for rimsulfuron and its IN-70941, 70942, and E-9260 

degradates.

DuPont Comments: DuPont will consider submitting ECM and ILV data for soil for rimsulfuron and its 

degradates to the Agency if they are required as part of a data callin.

EFED Response to Comment:

EFED has submitted these data needs to PRD for action.

------------------------------

835.6200 Aquatic field dissipation study: 

State of the art Environmental Chemistry Method (ECM) for trace residues in water and Independent 

Laboratory Validation (ILV) is requested for rimsulfuron and its IN-70941, 70942, and E-9260 

degradates.

DuPont Comments: DuPont will consider submitting ECM and ILV data for water for rimsulfuron and 

its degradates to the Agency if they are required as part of a data callin.

EFED Response to Comment:

EFED has submitted these data needs to PRD for action.

------------------------------

850.1350 Aquatic invertebrate life-cycle (marine): 

Results from the review of the submitted

freshwater study may negate the need for additional data.

DuPont Comments: DuPont looks forward to the completed Agency review of MRID Nos. 43472701 and 

43472702.

EFED Response to Comment:

A review of these data will be forthcoming.

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850.1400 Estuarine/marine fish early life stage: 

Results from the review of the submitted freshwater study may negate the need for additional data.

DuPont Comments: DuPont looks forward to the completed Agency review of MRID Nos. 43472703, 

43472704 and 43472705.

EFED Response to Comment:

A review of these data will be forthcoming.

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850.4100 Terrestrial plant toxicity, seedling emergence, Tier II: 

The studies that were submitted were conducted with TGAI. The use of a TEP is required. In addition, 

NOAEL values were not determined for the most sensitive species. Tier II seedling emergence studies 

should be conducted for 6 dicots and 4 monocots with a TEP.

DuPont Comments: DuPont will consider submitting seedling emergence data for a rimsulfuron typical 

end use product to the Agency if they are required as part of a data call-in.

EFED Response to Comment:

EFED has submitted these data needs to PRD for action.

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850.4150 Terrestrial plant toxicity, vegetative vigor, Tier II: 

The studies that were submitted were conducted with TGAI. The use of a TEP is required. In addition, 

NOAEL values were not determined for the most sensitive species. Tier II vegetative vigor studies should 

be conducted for 6 dicots and 4 monocots with a TEP.

DuPont Comments: DuPont will consider providing vegetative vigor data for a rimsulfuron typical end 

use product to the Agency if they are required as part of a data call-in.

EFED Response to Comment:

EFED has submitted these data needs to PRD for action.

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835.4100 Aerobic soil metabolism: 

Data have been submitted (MRID No. 48332003) and are under review.

DuPont Comments: DuPont looks forward to the completed Agency review of this study.

EFED Response to Comment:

A review of these data will be forthcoming.

------------------------------

835.4300 Aerobic aquatic metabolism: 

Data have been submitted (MRID No. 45490802) and are under review.

DuPont Comments: DuPont looks forward to the completed Agency review of this study.
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EFED Response to Comment:

A review of these data will be forthcoming.

------------------------------

850.1300 Aquatic invertebrate life-cycle (freshwater): 

Data have been submitted (MRID Nos. 43472701 and 43472702) and are under review.

DuPont Comments: DuPont looks forward to the completed Agency reviews of these studies.

EFED Response to Comment:

A review of these data will be forthcoming.

------------------------------

850.1400 Freshwater fish early life-stage: 

Data have been submitted (MRID Nos. 43472703, 43472704 and 43472705) and are under review.

DuPont Comments: DuPont looks forward to the completed Agency reviews of these

studies.

EFED Response to Comment:

A review of these data will be forthcoming.