toxic than the parent. Therefore, considering the available metabolite data, DAS respectfully requests that EFED reconsiders th eir approach to the TTR analysis performed in this draft risk

assessment.

EFED Response: While the cited Lemna plant toxicity data for two of the degradates used in the TTR approach could inform a refinement to th e TTR estimated environmental concentrations (EECs) for aquatic plants, risk quotients (RQs ) using parent-only EECs exceeded the level of concern (LOC) for aquatic plants (RQs: non-listed ≤ 3.2; listed ≤ 5.4; LOC = 1). Therefore, the overall risk profile for plants wi ll not appreciably change by inclus ion of this additional toxicity data. At this time, the cited Lemna toxicity data is not requeste d. Furthermore, the availability of this additional plant degradate toxicity data is not sufficient evidence to refine the TTR approach for aquatic animals.

DAS Comment: In the “Terrestrial field dissipation” property, some values in the table appear to not match those presented in the referenced studies/MRIDs.

EFED Response: Values in the referenced table were taken from the “Environmental Fate and Ecological Risk Assessment for the Section 3 New Uses of Isoxaben on Bearing Nut Trees and Vineyards” (D341496). The values cited in DAS co mments and the values presented in the Risk

Assessment have both been referenced in EPA records and both sufficiently characterize the dissipation of isoxaben.

DAS Comment: An additional aerobic soil degradation study was submitted as part of the 2011 DCI which included a single US soil. The DT50 was de termined to be 96 days in this sandy clay

loam soil.

EFED Response: The referenced aerobic soil metabolism study (MRID 49090101) is

considered and referenced in Table 7 of the Ri sk Assessment, the exposure modeling inputs, but is not included in Table 5, the environmental fate data summary. MRID 49090101 is fully considered in the Registration Review Risk Assessment.

DAS Comment: The aerobic degradation of isoxaben was also investigated in one U.S. soil in which a half-life of 96 days was observed (M RID 49090101). As in the previous aerobic soil degradation study in foreign soils (MRID 47140004), the only major degrad ate identified in the study was hydroxy isoxaben. In addition, characterizat ions and classifications of the foreign and U.S. soils used in these studies were outlined in each respective study report.

EFED Response: As addressed above, MRID 49090101 is fu lly considered in the Registration

Review Risk Assessment.

DAS Comment: While the NOEL for the chronic ma mmalian reproduction study is 40 mg/kgbw, this is based on statistically significant pa rental body and liver wei ght changes. These bodyand organ weight changes are not ecologically-relevant as there were no treatment-related effects on mating performance or fertilit y, thus population levels would not be affected. Additionally, as stated on page 48, there were no effects on de velopment or maternal toxicity up to 1000 mg/kg/day in rat and rabbit developmental studi es. Therefore, the developmental NOEL should be set at 200 mg/kg-bw and there are no LOC exceedances for any mammalian size class when using a developmental NOEL of 200 mg/kg-bw.

EFED Response: While effects on reproductive paramete rs (mating performance or fertility) may not have been observed in the mammalian toxicity study at a dos e where parental body weight was affected, a reduction in body weight in a mammal in the environment could impact its overall fitness and could have adverse conseq uences on reproductive behavior (e.g., ability to find/attract mate, prepare nesti ng site, source food for offspring). Therefore, the NOAEL value of 40 mg/kg-bw is still considered a relevant endpoint for calculation of RQs in the screeninglevel ecological risk assessment. RQs exceed the LOC when using both the maximum and minimum single application rate or when using mean EECs (as opposed to the upper-bound EECs). It is noted that at the parental t oxicity LOAEL (200 mg/kg-bw), based on decreased female body weight gain ( ↓ 16%)/body weights ( ↓ 6%), there were no impacts on offspring or reproductive parameters, and as characterized in the risk assessment, there are no LOC exceedances when comparing EECs to the parental LOAEC/developmental NOAEL. In the screening-level assessment for mammals (and birds), an assumption is that the animals forage for food exclusively on the treated field a nd they consume a single food type ( i.e ., short grass). These assumptions may not be representative of all environmental scenarios. As the distance increases from the treated area, the residues will also reduce, thereby lower the RQ values. The distance from the treated area to be below the pa rental NOAEC, based on spray drift, is 20 feet (attachment #1). Therefore, while there are uncer tainties regarding potential chronic risk to mammals, the risks of chronic effect s cannot be entirely discounted.Attachment #1

AgDrift (v2.1.1) spra y drift calculation Aerial application, default dr oplet size fine to medium

Fraction of applied = LOC/RQ = 1/3.84 (highest mammalian dose-based RQ) = 0.26