toxic than the parent. Therefore, considering the available metabolite data, DAS respectfully 

requests that EFED reconsiders their 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 the 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 will not appreciably change by inclusion of this additional toxicity 

data. At this time, the cited Lemna toxicity data is not requested. 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 comments 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 determined 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 Risk 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 (MRID 49090101). As in the previous aerobic soil 

degradation study in foreign soils (MRID 47140004), the only major degradate identified in the 

study was hydroxy isoxaben. In addition, characterizations 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 fully considered in the Registration 

Review Risk Assessment. 

DAS Comment: While the NOEL for the chronic mammalian reproduction study is 40 mg/kgbw, this is based on statistically significant parental body and liver weight changes. These body 
and organ weight changes are not ecologically-relevant as there were no treatment-related effects 

on mating performance or fertility, thus population levels would not be affected. Additionally, as 

stated on page 48, there were no effects on development or maternal toxicity up to 1000 

mg/kg/day in rat and rabbit developmental studies. 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 parameters (mating performance or fertility) 

may not have been observed in the mammalian toxicity study at a dose 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 consequences on reproductive behavior (e.g., ability to 

find/attract mate, prepare nesting 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 toxicity 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 and 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 parental NOAEC, based on spray drift, is 20 feet 

(attachment #1). Therefore, while there are uncertainties regarding potential chronic risk to 

mammals, the risks of chronic effects cannot be entirely discounted. 

 
Attachment #1 

AgDrift (v2.1.1) spray drift calculation 

Aerial application, default droplet size fine to medium 

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