Comparison of available benchmark dose softwares and models using trichloroethylene as a model substance.

By using trichloroethylene as a model substance the U.S. EPA benchmark dose software was compared to the software by Crump and the software by Kalliomaa. Dose-response and dose-effect data on the liver, kidneys, central nervous system (CNS), and tumours were selected for the evaluation. Based on the present study the U.S. EPA software is preferable to the other softwares for dichotomous data. A wider range in benchmark doses was often observed for dichotomous data when the numbers of dose levels were limited. The log-logistic model in most cases gave the best fit when ranking the dichotomous models. In addition, the log-logistic model often implied a more conservative benchmark dose. For continuous data it was more difficult to find a model describing the data. The softwares by Kalliomaa and by the U.S. EPA offered the best opportunities for benchmark dose modelling of continuous data. Flexible models, like the Hill- and the Mult model, are needed for S-shaped continuous data but these models demand more dose levels in order to describe the data. Since the number of dose levels are important for model selection study design is important and should be further evaluated.

[1]  H. Akaike,et al.  Information Theory and an Extension of the Maximum Likelihood Principle , 1973 .

[2]  Salomon Sand,et al.  Evaluation of the benchmark dose method for dichotomous data: model dependence and model selection. , 2002, Regulatory toxicology and pharmacology : RTP.

[3]  H Tsuruta,et al.  Inhalation carcinogenicity of trichloroethylene in mice and rats. , 1983, Industrial health.

[4]  C. Elcombe,et al.  Biochemical, histological, and ultrastructural changes in rat and mouse liver following the administration of trichloroethylene: possible relevance to species differences in hepatocarcinogenicity. , 1985, Toxicology and applied pharmacology.

[5]  Kenny S. Crump,et al.  Calculation of Benchmark Doses from Continuous Data , 1995 .

[6]  K Kalliomaa,et al.  A new model function for continuous data sets in health risk assessment of chemicals using the benchmark dose concept. , 1998, Regulatory toxicology and pharmacology : RTP.

[7]  D W Gaylor,et al.  Issues in qualitative and quantitative risk analysis for developmental toxicology. , 1988, Risk analysis : an official publication of the Society for Risk Analysis.

[8]  C. Kimmel,et al.  Dose-response assessment for developmental toxicity. II. Comparison of generic benchmark dose estimates with no observed adverse effect levels. , 1994, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[9]  C. Elcombe.  Species differences in carcinogenicity and peroxisome proliferation due to trichloroethylene: a biochemical human hazard assessment. , 1985, Archives of toxicology. Supplement. = Archiv fur Toxikologie. Supplement.

[10]  K S Crump,et al.  A new method for determining allowable daily intakes. , 1984, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[11]  B. Merrick,et al.  Differing hepatotoxicity and lethality after subacute trichloroethylene exposure in aqueous or corn oil gavage vehicles in B6C3F1 Mice , 1989, Journal of applied toxicology : JAT.

[12]  W. Stott,et al.  The pharmacokinetics and macromolecular interactions of trichloroethylene in mice and rats. , 1982, Toxicology and applied pharmacology.

[13]  Elaine M. Faustman,et al.  Review of noncancer risk assessment: Applications of benchmark dose methods , 1997 .

[14]  K. Victorin,et al.  Application of the benchmark method to risk assessment of trichloroethene. , 1995, Regulatory toxicology and pharmacology : RTP.

[15]  J. Buben,et al.  Delineation of the role of metabolism in the hepatotoxicity of trichloroethylene and perchloroethylene: a dose-effect study. , 1985, Toxicology and applied pharmacology.

[16]  R J Kavlock,et al.  A simulation study of the influence of study design on the estimation of benchmark doses for developmental toxicity. , 1995, Risk analysis : an official publication of the Society for Risk Analysis.

[17]  D. Henschler,et al.  Carcinogenicity study of trichloroethylene by longterm inhalation in three animal species , 1980, Archives of Toxicology.

[18]  B. Holmquist,et al.  Trichloroethylene: further studies of the effects on body and organ weights and plasma butyrylcholinesterase activity in mice. , 2009, Acta pharmacologica et toxicologica.

[19]  A. Greenwell,et al.  Application of microencapsulation for toxicology studies. II. Toxicity of microencapsulated trichloroethylene in Fischer 344 rats. , 1987, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[20]  Wout Slob,et al.  Few large, or many small dose groups? An evaluation of toxicological study designs using computer simulations , 1997 .

[21]  C. Maltoni,et al.  Long‐Term Carcinogenicity Bioassays on Trichloroethylene Administered by Inhalation to Sprague‐Dawley Rats and Swiss and B6C3F1 Mice , 1988, Annals of the New York Academy of Sciences.