# Commission Directive 2004/73/EC of 29 April 2004 adapting to technical progress for the twenty-ninth time Council Directive 67/548/EEC on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances (Text with EEA relevance), Division 1.5.4: Dose selection

Extent: E+W+S+N.I.

Dose levels should be selected by taking into account any previously observed toxicity and kinetic data available for the test compound or related materials. The highest dose level should be chosen with the aim of inducing neurotoxic effects or clear systemic toxic effects. Thereafter, a descending sequence of dose levels should be selected with a view to demonstrating any dose-related response and no-observed-adverse effect (NOAEL) at the lowest dose level. In principle, dose levels should be set so that primary toxic effects on the nervous system can be distinguished from effects related to systemic toxicity. Two to three intervals are frequently optimum and addition of a fourth test group is often preferable to using very large intervals (e.g., more than a factor of 10) between dosages. Where there is a reasonable estimation of human exposure this should also be taken into account.

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Source: https://www.legislation.gov.uk/eudr/2004/73/annex/2H/division/B.43/division/1/division/1.5/division/1.5.4 (the official version)
Page: https://openlegislation.uk/eu-directive-2004-73/annex-2H/division-B.43/division-1/division-1.5/division-1.5.4
Contains public sector information licensed under the Open Government Licence v3.0. Source: legislation.gov.uk, The National Archives.