ToxSci Advance Access published online on December 1, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfj057
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Institute of Environmental Medicine, Karolinska Institutet, P.O. Box 210, SE-17177 Stockholm, Sweden
* To whom correspondence should be addressed. The benchmark dose (BMD) method has been recommended to replace the NOAEL approach in health risk assessment of chemical substances. In the present paper developments in BMD analysis from continuous experimental data are proposed. The suggested approach defines the BMD as the dose where the slope of the S-shaped dose-response relationship changes the most in the low-dose region. This dose resides in a region where the sensitivity to chemical exposure may start to change noticeably. It is shown that the response (defined as a % change relative to the magnitude, or size, of response) corresponding to the dose where the slope changes the most depends on the geometrical shape of the dose-response curve; the response becomes lower as the curve becomes more asymmetrical and threshold-like in the low-dose region. Given a symmetrical case, described by the Hill function, the response associated with the critical dose level becomes 21 % (defined as a % change relative to the magnitude, or size, of response). According to a limiting case of asymmetry and threshold-like characteristics, reflected by a Gompertz curve, the response corresponding to the dose of interest becomes as low as 7.3 % (defined as a % change relative to the magnitude, or size, of response). Use of a response in the range of 5 - 10 % when estimating the BMD conservatively accounts for uncertainties associated with the proposed strategy, and may be appropriate in a risk assessment point of view. The present investigation also indicated that a BMD defined according to the suggested procedure may be estimated more precisely relative to BMDs defined under other approaches for continuous data.
Received August 9, 2005
Accepted November 19, 2005
Risk Assessment
Identification of a Critical Dose Level for Risk Assessment: Developments in Benchmark Dose Analysis of Continuous Endpoints
Salomon Sand 1 *,
Dietrich von Rosen 2,
Katarina Victorin 1,
and
Agneta Falk Filipsson 3
2 Department of Biometry and Informatics, Swedish University of Agricultural Sciences, P.O. Box 7032, SE-750 07 Uppsala, Sweden
3 Swedish Chemicals Inspectorate, P.O. Box 2, SE-172 13 Sundbyberg, Sweden
Salomon Sand, E-mail: Salomon.Sand{at}imm.ki.se
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  T. L. Lassiter and S. Brimijoin A Method to Determine Precise Benchmark Doses for Carbamate Anticholinesterases Toxicol. Sci., March 1, 2007; 96(1): 154 - 161. [Abstract] [Full Text] [PDF]
|
|