MEMORANDUM

SUBJECT :

TO:

FROM:

THROUGH: UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON D.C., 20460

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

DP Barcode: 428005 PC Code: 118205 Da t e: 09/04/2015

Lufenuron: Response to Comments Received on the Problem Formulation

Bonnie Adler
, Chemical Review Manage r Linda Arrington, Chief Risk Management and Implementation Branch 5 Pest i cide Re-Evaluat i on Div i sion

Rosanna L ou i e
-Juzwiak
, RAPL Env i ronmental Risk Br a nch 3 Environmental Fate a nd Effects Div i sion

Dana Spatz, Branch Chief EnvironmentalRiskBranch3 Environmental Fate and Effects Division

The Environmental Fate and Effects Division (EFED) reviewed commen t s received on the Lufenuron Problem Formulation that was completed as part of registration review. Comments were received from the Physicians Committee for Responsible Medicine, and the technical registrant, Syngenta Crop Protect i on LLC. Below is a summary of the comments and EFED's responses.

Environmental Fate

Syngenta Comment: "Please include all five so i l water partition coefficients listed in MRID 45853203

. .. "

EFED Response : EFED appreciates the editorial comment

- one of the values was inadvertently omitted from the list. All appropriate values will be considered in the risk assessment.

Ecotoxicity

Physicians Committee for Responsible Medicine Comment : recommend consideration of the OECD Test Gu i del i ne 223. Avian Acute Oral Tox i city Test instead of EPA Gu i deline 850

. 2100 in the interest of reducing the number of animals used

. .. and cited data from the European Food Safety Authority

### reporting an avian reproductive endpoint for Bobwhite quail of 19 mg/kg bw/day, encouraging EPA to consider the study.

EFED Response : EFED appreciates the comment and will consider all available data as appropriate in support of the risk assessment. Careful consideration of the limitations and appropriateness of the OECD Test Guideline 223 is needed for a given test chemical and species. Namely, TG 223 recommends using test species with low background mortality and a low propensity to regurgitate (historically, these would be the Bobwhite quail and Japanese quail). Thus, th is test design may not be appropriate for use with other test species ( e.g. , passerines). The specific considerations are described in the EFED guidance document: “ Guidance for Classifying Studies Conducted Using the OECD Test Guideline 223 (TG223) (Acute Avian Oral Sequential Dose Study) .”

Syngenta Comment : the current [market] label states that the amount per station is 30 grams of bait, containing 0.15% (1,500 ppm) lufenuron. Stations are placed approximately 10 feet (ft) apart. For example, a 200-linear house (2,000 square ft) could theo retically have up to 20 stations, but 12 stations would suffice.

EFED Response : EFED appreciates the information and will cons ider this exposure in the risk assessment.

Syngenta Comment regarding avian acute oral toxicity and passerine species : while there would be uncertainty in the sensitivity of a passerine versus the mallard and bobwhite quail, they believe that if no mortality is observed in the sta ndard test species and the adjusted LD 50 

### value for a 20-gram bird results in a RQ that passes the scr eening level assessment (acute risk ca lculations provided), then testing with a passerine species is not expected to provide new information of value concerning avian toxicity from acute exposures. They provide an analysis toestimate a dose-based EEC of 123 mg/kg-bw day (using empirical data on hexaflumuron mass in a termite), compared to an adjusted LD 50

### for a 20-gram bird using the Mineau factor. While this analysis indi cates that the acute RQ would be slightly exceeded for listed birds (0.12), there would be a very low likelihood to achieve this exposure (dose) given that this dose is equivalent to over 76,000 contaminated termites that would need to be ingested.

EFED Response : EFED agrees with this rationale with rega rds to acute exposure for birds, and believes that a new acute oral study conducted using a passerine is not needed at this time to inform on acute risks to birds.

Syngenta Comment regarding avian chronic toxicity : using the NOEC from current avian reproduction studies ( i.e. , 200 ppm), based on the predicted dietary EECof 107 ppm (using measured hexaflumuron termite concentrations of 320 ng/termite, which also assumes a 0.5% concentration, higher than the 0.15% concentration in lufenuron baits), the chronic RQ would be 0.54, below the LOC of 1. Even if assuming a NOEC for lufenuron 4x lower ( i.e. , 50 ppm), this would be equivalent to almost 3,600 termites that a 20-gram bird would need to consume, or 47% of its daily food intake. Finally, when comparing using the hexaflumuron avian reproduction endpoint of 29.4 mg/kg-diet day, this would be equivalent to a bird consuming 2,113 termites a day. They also rationalize that given that both the bobwhite quail and mallard studies resulted in similar effects in chick survival at similar concentrations (from 200 to 400 ppm), it is unlikely that repeating th e studies would result in significantly lower NOECs. Therefore, they conclude that lufenuron poses similar or lower chronic risk to avian species than hexaflumuron, and therefore, conclusions regarding la ck of risk to birds may be similarly made for lufenuron.

### EFED Response : EFED generally agrees with the analysis pr esented to estimate potential exposure. While there is the potential for co-occurrence of contaminat ed termites being available to insectivorous birds, there is a low likelihood that a bird species would be consuming ~30% (Syngenta’s analysis based on hexaflumuron termite concentration) of its diet solely from contaminated termites (translating to over 2,000 termites daily). Even when considering the existing hexaflumuron chronic avian NOEC of 29.4 mg/kg-diet, using the information on noviflumuron concentration in termites (Karr et al. 2004) referenced by Dow, adjusted to reflect the lufenuron concentration in stations (0.15%), and the hexaflumuron mallard reproduction NOEC, there is a potential to exceed the chronic LOC:

Termite concentration* of chemical (1% noviflum uron) = 0.001098 mg/termite (Karr et al. 2004) Adjusted for lufenuron bait stations (0.15%) = 0.0001647 mg/termite Termite fresh weight = 3 mg (Zhou et al . 2008) Concentration in termite diet = 0.0001647 mg / 0.000003 kg = 54.9 mg/kg

Assuming a very conservative assumption that 100% of the diet is termites, when compared to the hexaflumuron avian reproduction NOEC (for the mallard) of 29.4 mg/kg-diet, the chronic RQ would be 1.86. The analysis below describes what this represents in terms of number of termites needed to reach this exposure:
Target percentage of diet = (1/1.86)(100) = 54% Termite mass (daily consumption x Target % Diet) = 23g/day x 0.54 = 12.42 g Number of termites (12.42 g X 1000 mg/g)/3 mg = 4,140 termites.

Based on these analyses, although an empirical NOAEC for lufenuron has not been determined, EFED can concur that an additional avian reproduction te st (OCSPP Guideline 850.2300) would be of low value relative to the currently-registered uses, and that a new one is not needed at this time.

References:

Karr, L., Sheets, J., King, J. E., and J.E. Dripps. Laboratory Performance and Pharmacokinetics of the Benzoylphenylurea Noviflumuron in Eastern Subterranean Termites (Isoptera: Rhinotermitidae). April 2004. Journal of Economic Entomology, 97 (2): 593-600. Referenced in Dow AgroSciences' Comments to U.S. EPA's Problem Formulation and Related Documents Posted in the Docket for Noviflumuron Registration Review. Report ID JT112114. November 21, 2014.

Zhou, X., Wheeler, M.M. Wheeler, F.M. Oi, and M.E. Scharf. 2008. RNA interference in the termite Reticulitermes flavipes through ingestion of double-stranded RNA. Insect Biochemistry and Molecular Biology, 38 (8): 805-815. Referenced in Dow AgroSciences' Comments to U.S. EPA's Problem Formulation and Related Documents Posted in the Docket for Noviflumuron Registration Review. Report ID JT112114. November 21, 2014.