Page 2 of 5 BMD Analysis

The toxicity endpoint for short-term incide ntal oral exposures to tetramethrin was selected from a two-generation rat reproducti on study with 1 litter per generation (MRID 00161842). The NOAEL is 500 ppm and the LOAEL is 3000 ppm based on decreased body weight and food consumption in both sexes of F0 and F1 parental animals and decreased pup body weight during lactation.

A BMD is defined as an exposure due to a dose of a substance associat ed with a specified low incidence of risk, generally in the range of 1% to 10%, of a hea lth effect; or the dose associated with a specified measure or change of a biological effect. This dose is estimated using statistical methods for fitting curves to experimental data.

EPA’s Benchmark Dose Software (BMDS version 1.4.1) was used for the BMD analysis of body weight data from the tetramethrin rat reproduction study. A benchmark dose (BMD) approach is used to more accurately estimate a po int of departure (POD) for the observed effects. The BMDS continuous models were selected to model the data being evaluated based on the continuous nature of body weight data. BMDS lin ear, polynomial, power and Hill models were used to derive the BMD 5 , the estimated benchmark doses that results in 5% body weight change, and the BMDL 5 , the lower 95% confidence interval on the BMD 5 , for the data evaluated. The BMDS continuous model default option of rela tive deviation was used for the benchmark response (BMR) type, with a co rresponding BMR factor of 0.05 (5 %) used as a basis for BMD and BMDL derivation. The default benchmark response (BMR) level of 5% is considered reasonable for determining a point of depart ure for body weight effects because body weight changes below 5% are ordinarily not associated with adverse eff ects. Since it is particularly important that the data be adequately modeled for BMD calculation, a p-value of 0.1 was used to assess goodness of fit.

Study Used for BMD Analysis

Pence, D.; Wolfe, G.; Kulwich, B. (1986) Two-generation Reproduction Study in Rats: Neopynamin Forte: Final Report: Project No. 34 3-147. Unpublished study prepared by Hazleton Laboratories America, Inc. 418 p. MRID: 00161842

Effects Modeled

The submitted analysis modeled 24 endpoints based on decreased body weights of males and females during the F0 and F1 growth phase s, decreased body wei ghts of females during gestation and lactation of the F0 and F1 genera tion, decreased body weight of males and females during the 30-day postweaning period of the F1 generation, and decreased pup body weight in the F1 and F2 litters. Dose-response input data sets used in the analys is are provided in the registrant’s submi ssion (MRID 47921601).Page 3 of 5 Recommended BMDL

BMDLs are selected based on absolute model fit (goodness of fit statis tics i.e., P-value > 0.10), comparative model fit (Aka ike Information Crite ria (AIC)), and visual inspection of modeled data fit. The registrant selected a BMDL 5 of 611 ppm (61 mg/kg/day) for use in the tetramethrin risk assessment for incidental oral exposure based on th e result generated by the polynomial model for the effect of decreased offspring body weight on day 21 in the F0F1 generation. HED agrees with the selected endpoint. It should be noted that the registrant used a conversion factor of 0.1 to convert from ppm to mg/kg/day. In contrast , HED used a conversion factor of 0.05 in its toxicity and risk assessments for tetramethri n. HED agrees that a conversion factor of 0.1 is more appropriate for rat repr oduction studies i.e., it generally assumed that a young adult rat consumes 10% of its bodyweight. Given use of the appropriate conversion factor, HED notes that overall, the results of the BMD analysis on the bodyweight effects modeled generally support th e NOAEL of 500 ppm used as the POD for the tetramethrin incidental oral exposure assessment. The statisti cal and graphic results fo r the selected modeled endpoint are provided below. A co mplete summary of results of th e BMD analysis for all of the modeled effects is provided in registrant’s submission.

Offspring body weight on day 21 in females in the F0F1 generation (Litter average) Model BMD 5 BMDL 5 P-Value AIC Linear 959 721 0.2282 346 Polynomial 2° 2,207 611 0.2255 346 Power 2,753 770 0.1874 346 Hill 2,529 502 NA 348

28 30 32 34 36 38

0 500 1000 1500 2000 2500 3000Mean Response

dose Linear Model with 0.95 Confidence Level

11:17 11/04 2009 BMD BMDL LinearPage 4 of 5 28 30 32 34 36 38

0 500 1000 1500 2000 2500 3000Mean Response

dose Polynomial Model with 0.95 Confidence Level

11:19 11/04 2009 BMD BMDL Polynomial

28 30 32 34 36 38

0 500 1000 1500 2000 2500 3000Mean Response

dose Power Model with 0.95 Confidence Level

11:21 11/04 2009 BMD BMDL PowerPage 5 of 5 28 30 32 34 36 38

0 500 1000 1500 2000 2500 3000Mean Response

dose Hill Model with 0.95 Confidence Level

11:16 11/04 2009 BMD BMDL Hill