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 

Dat e: 09/04/2015 

Lufenuron: Response to Comments Received on the Problem Formulation 

Bonnie Adler, Chemical Review Manager 

Linda Arrington, Chief 

Risk Management and Implementation Branch 5 

Pesticide Re-Evaluation Division 

Rosanna Louie-Juzwiak, RAPL 

Environmental Risk Branch 3 

Environmental Fate and Effects Division 

Dana Spatz, Branch Chief 

EnvironmentalRiskBranch3 

Environmental Fate and Effects Division 

The Environmental Fate and Effects Division (EFED) reviewed comment 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 

Protection LLC. Below is a summary of the comments and EFED's responses. 

Environmental Fate 

Syngenta Comment: "Please include all five soil 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 

Guideline 223. Avian Acute Oral Toxicity Test instead of EPA Guideline 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, this 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 theoretically have up to 20 stations, but 12 stations 

would suffice. 

EFED Response: EFED appreciates the information and will consider 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 standard test species and the adjusted LD50 value for a 20-gram bird 

results in a RQ that passes the screening level assessment (acute risk calculations 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 to estimate a dose-based EEC of 123 mg/kg-bw day 

(using empirical data on hexaflumuron mass in a termite), compared to an adjusted LD50 for a 20-gram 

bird using the Mineau factor. While this analysis indicates 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 regards 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 EEC of 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 the 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 lack of risk to birds may be similarly made for 

lufenuron. 
EFED Response: EFED generally agrees with the analysis presented to estimate potential exposure. While 

there is the potential for co-occurrence of contaminated 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% noviflumuron) = 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 test (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.