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BMD Analysis

The toxicity endpoint for short-term incidental oral exposures to tetramethrin was 

selected from a two-generation rat reproduction 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 associated with a specified 

low incidence of risk, generally in the range of 1% to 10%, of a health 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 point 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 linear, polynomial, power and Hill models were 

used to derive the BMD5, the estimated benchmark doses that results in 5% body weight change, 

and the BMDL5, the lower 95% confidence interval on the BMD5, for the data evaluated. The 

BMDS continuous model default option of relative deviation was used for the benchmark 

response (BMR) type, with a corresponding 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 departure for body weight effects because body weight 

changes below 5% are ordinarily not associated with adverse effects. 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. 343-147. Unpublished study prepared by Hazleton 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 phases, decreased body weights of females during 

gestation and lactation of the F0 and F1 generation, 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 analysis are provided in the 

registrant’s submission (MRID 47921601). 
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Recommended BMDL

 BMDLs are selected based on absolute model fit (goodness of fit statistics i.e., P-value > 

0.10), comparative model fit (Akaike Information Criteria (AIC)), and visual inspection of 

modeled data fit. The registrant selected a BMDL5 of 611 ppm (61 mg/kg/day) for use in the 

tetramethrin risk assessment for incidental oral exposure based on the 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 tetramethrin. HED agrees that a conversion 

factor of 0.1 is more appropriate for rat reproduction 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 the NOAEL of 500 ppm used as the POD for the tetramethrin 

incidental oral exposure assessment. The statistical and graphic results for the selected modeled 

endpoint are provided below. A complete summary of results of the 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 BMD5 BMDL5 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 

 

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Mean Response

dose

Linear Model with 0.95 Confidence Level

11:17 11/04 2009

BMDL BMD

 

Linear
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Mean Response

dose

Polynomial Model with 0.95 Confidence Level

11:19 11/04 2009

BMDL BMD

 

Polynomial

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Mean Response

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Power Model with 0.95 Confidence Level

11:21 11/04 2009

BMDL BMD

 

Power
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Mean Response

dose

Hill Model with 0.95 Confidence Level

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BMDL BMD

 

Hill