On December 22nd 2010, the site has been updated with physiological parameters published in 2010. A pilot study was performed in 2009, concerning a meta-analysis of the parameter values present in the database with more than one reference. The site has been extended with the results of the meta-analysis.

On December 23rd 2009, the site has been extended with a few physiological parameters for specific age stages, such as elderly, premature and foetuses.

On December 23rd 2008, the site has been extended with data on kidney and lung. Since January 30th 2009 this new data can also be viewed in the Interspecies part.

On December 19th 2007, the site has been extended with comparable data on children in various age stages and data on juvenile animals.

On April 10th 2007, new features have been added to the organ pages under the Interspecies part of the site: data may be downloaded as MS Excel files and you are able to view the data in your preferred way by filtering rows and columns.

On March 22nd 2007, new information has been added to this site. In the Intraspecies part two new columns have been added to the tables: Age Class and Remark. In the Interspecies part only the column Age Class has been added.

Since the launch of this RIVM website in January 2006, information was provided on anatomical and physiological parameter values, as well as parameter values relevant for the metabolism of xenobiotics in humans and various species frequently used in toxicity testing. Focus is on parameters in organs and tissues relevant for kinetics following oral exposure.

In 2011, it is foreseen to update the site with physiological data and it is intended to add more results of the meta-analysis.

Lists of parameters and parameter values can be accessed through the Intraspecies and Interspecies options in the left-hand column on every webpage.

Click on the Intraspecies option to choose a species and an organ. You will be led to a page with the link: Parameter list (in html). Clicking on this link leads you to a table for that specific species and organ.

Click on the Interspecies option to choose an organ. You will be led to a page with the link: Parameter list in MS-Excel file. Clicking on this link leads you to a table for comparing the parameter values of all species/strains and ages with that specific organ.

Numerous studies in which a variety of compounds were tested have demonstrated that interspecies differences can be substantial, hampering reliable extrapolation of the results to the human situation. There are of course many differences between animal species themselves as well as between animals and man. These differences may influence the kinetics and/or dynamics of a compound, e.g. long nose (inhalatory exposure) and tails, furry (topical application), diet, coprophagy, intestinal anatomy and physiology, differences in metabolic pathways, extent of biliary excretion, body surface relative to body weight, metabolic rates, etc. There are, on the other hand, also various similarities between animals and humans, e.g. liver as important metabolising organ, liver and kidney as important for excretory organs, comparable circulatory systems and specialised mechanisms for elimination of xenobiotics.

The aim of this website is to gain insight into the impact of anatomical and physiological (including biotransformation) differences between species and within species on the kinetics (especially on oral bioavailability) of xenobiotics. This insight may lead to improved species selection and subsequently to improved animal-human extrapolation.

The purpose of the meta-analysis is to summarize the reported data for a given kinetic parameter by a single mean value, together with a measure of the associated uncertainty in that value. The uncertainty will be smaller (larger) when the number of available studies reporting a particular parameter is larger (smaller), and when the variation among studies is smaller (larger). If reported, the sample sizes (N) as used in the various studies are taken into account, by giving studies with a larger N more weight in calculating the overall mean value over studies.  In particular,

where y_i denotes the arithmetic or geometric (see below) mean of study i, and N_i the sample size for that study.

A practical problem is that most studies report arithmetic means, while others report geometric means. The geometric mean is a preferable mean value for representing the 'typical' value of a kinetic parameter, and therefore a reported arithmetic mean (AM) is translated into a geometric mean (GM), if possible, which is the case if the studies report the standard deviations (SD) as well. This is done by first calculating the coefficient of variation (CV):

and then the geometric mean (GM) by:

The underlying assumption is that the individual observations (within a study) are log-normally distributed.

If the GMs can be calculated, they are used in expression (1) for calculating the overall (geometric) mean. If, however, one of the reported AMs cannot be translated into its GM, then the AMs for all studies are used. So, there are three possibilities (in order of preference) for evaluating expression (1): use reported GMs, use GMs derived from AMs, or use the reported AMs.

The uncertainty in the overall mean obtained by expression (1) is expressed as a factor, indicating by how much the “true” value could be lower or higher. This factor is calculated by first calculating the confidence interval for the overall study mean, on log-scale, in the usual way, i.e., divide the standard deviation among studies by the square root of the number of studies, and multiply that value by student’s t for deriving the lower bound of the confidence interval (at one-sided 95%-confidence level). Back-transforming the difference between the overall mean and the just derived lower confidence bound (both on log-scale) results in the factor expressing the uncertainty in the overall mean.