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Acubase – on-line system for high
quality acute toxicity data acquisition
and management
R. Rzepka1, R. Rudowski1, A. Kinsner3, D. Sladowski2, Ada
Kolman4, Thomas Cole 5, Christian Bieler 6, Pilar Prieto 3 and
Sandra Coecke 3
1.Department of Medical Informatics and Telemedicine, Medical University of Warsaw, Poland;
2.Department of Transplantology, Medical University of Warsaw, Warsaw , Poland;
3.European Centre for the Validation of Alternative Methods,
Institute for Health and Consumer Protection, E.C. Joint Research Centre, Ispra , Italy
4.Swedish Fund for Research without Animal Experiments, Sweden
5.European Chemicals Bureau, Institute for Health and Consumer Protection, E. C. Joint Research Centre,
Italy
6.Fraunhofer Institute for Toxicology and Experimental Medicine, Department Chemical Risk Assessment,
Hannover, Germany
Outline
1. Scientific background of A-Cute-Tox project
2.
3.
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4.
Software structure
The examples of user interface:
Chemical
In vitro
Animal
Human
Kinetics
Reports
Conclusion
Scientific background
of A-Cute-Tox project
A-Cute-Tox aims to improve the prediction of
acute toxicity using in vitro methods and, at
the same time, to signal which compounds
require further testing because their acute
toxicity cannot be properly predicted.
The concordance of in vitro cytotoxic
concentrations with in vivo LD 50 or human
lethal concentrations is estimated at present
as 70%.
A-Cute-Tox FP6 EU Research
Project for Alternative Testing
Project full title: Optimisation and pre-validation of
an in vitro test strategy for predicting human acute
toxicity.
A-Cute-Tox involves 37 partners from 13 countries
Acubase – system for data acquisition,
management and analysis – important part of ACute-Tox
WP 1 Generation of an in vivo database
and establishment of a depository of
reference compounds
WP 2 Generation of an in vitro database
Analysis and
integration of
in vitro/in vivo data
WP 4 New cell systems,
new endpoints
Alerts and correctors
in toxicity screening
WP 5 Role of ADE
WP 6 Role of metabolism
WP 3 Iterative amendment
of the testing strategy
WP7 Role of target organ
toxicity
• WP7.1 – neurotoxicity
• WP7.2 – nephrotoxicity
• WP7.3 – hepatotoxicity
WP 8 Technical optimisation of the
amended test strategy
WP 9 Prevalidation of the test
strategy
Acubase is on-line service
and database for storing and
quality management of
toxicity data
Software structure
Presentation
HTML Templates
Logic
PHP scripts
Code
PHP classes
(procedures, functions
and properties of objects)
Data
Sql database
1-st layer
2-nd layer
3-th layer
4-th layer
Requirements for communication
with Acubase
Any web browser XHTML 1.0 and CSS compliant
(Internet Explorer 5.5 +, Netscape Netscape 7.10 +,
Mozilla 1.4 +, Opera 6+)
Acubase is optimised for 1024x768 resolution
URL: https://acubase.amwaw.edu.pl/
Acubase entities
In vitro
tests
Human
cases
analysis
Chemicals
Animal
experiments
Optimisation
Kinetics
In silico
prediction
model
Basic tables relation in postgresql
Central object
ACUBASE SECURITY
Acubase is written as a multi-layered and multi-module application in
order to ensure:
• inaccessibility of passwords through the Internet
• resistance to common SQL Attacks (e.g. an SQL injection attack that "injects" or
manipulates SQL code by adding unexpected SQL to a query)
Furthermore Acubase is equipped with:
• alphanumeric passwords protection of the system and data
• encryption of every transmission between the database and the application
• SSH (Secure Shell) access as the only way to reach the operating system
(standard protections and various access levels typical to the UNIX family applied)
Last but not least:
Acubase is absolutely immune to notorious viruses and worms that plague
windows systems recently
Data entered before 31.03.2007
4000
3600
3500
3000
2209
2500
1663
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0
In vitro data
Human cases
Animal studies
The examples of user interface
Login view
At the moment access is restricted to ACuteTox partners.
In future it is planned to open the database to wider public
(scientists, clinicians, toxicologists, regulators, etc.)
97 reference
chemicals
in vitro data
human data
kinetics (in vivo,
in vitro, in silico)
animal in
vivo data
Chemical section
In vitro section
Result section of in vitro experiment form
Animal section
Human section
Human acute toxicity data
This database section represents human acute toxicity
data from a single poisoning, consisting of:
• toxic doses
• sub-lethal blood concentrations,
• lethal blood concentrations
• post-mortem blood concentrations
• symptoms and signs
• clinical treatment conditions
Kinetics and in silico section
Reports section
You can extract excel
files with data
Conclusions
•Acubase is a unique database, which integrates high quality
data on the acute toxicity from in vitro experiments, animal in
vivo studies and human poisoning cases.
•The system allows collection of diverse experimental data in a
standard format. Therefore the data from different experiments
can be compared and the best human toxicity prediction model
can be established.
•As raw experimental data are stored in the system it can be
regarded as GLP compliant.
•The system can be adapted to multicenter studies particularily
when different SOP‘s are used.
•In summary, Acubase serves as a central element of the
project with regard to reporting, management and analysis of
data in order to improve predictions of human acute toxicity and
substantially reduce animal experiments.
Thank you for
your attention