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ToxSci Advance Access published online on July 14, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh222
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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Received April 27, 2004
Accepted July 7, 2004

Risk Assessment

Dose-Response Modeling and Benchmark Calculations from Spontaneous Behavior Data on Mice Neonatally Exposed to 2, 2', 4, 4', 5-Pentabromodiphenyl Ether

Salomon Sand 1*, Dietrich von Rosen 2, Per Eriksson 3, Anders Fredriksson 3, Henrik Viberg 3, Katarina Victorin 1, Agneta Falk Filipsson 1

1 Institute of Environmental Medicine, Karolinska Institutet, P.O. Box 210, 17177 Stockholm, Sweden
2 Department of Biometry and Informatics, Swedish University of Agricultural Sciences, P.O. Box 7032, 750 07 Uppsala, Sweden
3 Department of Environmental Toxicology, Uppsala University, Norbyvägen 18A, S-75236 Uppsala, Sweden

* To whom correspondence should be addressed. E-mail: Salomon.Sand{at}imm.ki.se.


  Abstract

In this paper the benchmark dose (BMD) method was introduced for spontaneous behavior data observed in 2-, 5-, and 8-month-old male and female C57Bl mice exposed orally on postnatal day 10 to different doses of 2, 2' 4, 4', 5-pentabromodiphenyl ether (PBDE 99). Spontaneous behavior (locomotion, rearing, and total activity) was in the present work quantified in terms of a fractional response defined as the cumulative response after 20 minutes divided by the cumulative response produced over the whole 1h test period. The fractional response contains information about the time-response profile (which differs between the treatment groups) and has appropriate statistical characteristics. In the analysis male and female mice could be characterized by a common dose-response model, i.e. they responded equally to the exposure to PBDE 99. As a primary approach, the BMD was defined as the dose producing a 5 or 10% change in the mean fractional response. According to the Hill model, considering a 10% change the lower bound of the BMD for rearing, locomotion, and total activity was 1.2, 0.85, and 0.31 mg PBDE 99/kg body weight, respectively. A probability based procedure for BMD modeling was also considered. Using this methodology the BMD was defined as corresponding to an excess risk of 5 or 10% of falling below cut-off points representing adverse levels of fractional response.

Keywords: Spontaneous behavior; dose-response; benchmark dose; health risk assessment.
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S. Sand, D. von Rosen, K. Victorin, and A. Falk Filipsson
Identification of a Critical Dose Level for Risk Assessment: Developments in Benchmark Dose Analysis of Continuous Endpoints
Toxicol. Sci., March 1, 2006; 90(1): 241 - 251.
[Abstract] [Full Text] [PDF]


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