# 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 4: REFERENCES Extent: E+W+S+N.I. Table 1: Minimum numbers of animals needed per group when the neurotoxicity study is conducted separately or in combination whit studies Includes five animals selected for functional testing and detailed clinical observations as part of the neurotoxicity study NEUROTOXICITY STUDY CONDUCTED AS: Separate study Combined study with the 28-day study Combined study with the 90-day study Combined study with the chronic toxicity study Total number of animals per group 10males and 10 females 10males and 10 females 15males and 15 females 25males and 25 females Number of animals selected for functional testing including detailed clinical observations 10males and 10 females 10males and 10 females 10males and 10 females 10males and 10 females Number of animals selected per perfusion in situ and neurohistopathology 5males and 5 females 5males and 5 females 5males and 5 females 5males and 5 females Number of animals selected for repeated dose/subchronic/chronic toxicity observations, haematology, clinical biochemistry, histopathology, etc. as indicate in the respective Guidelines 5males and 5 females 10males and 10 females 20malesand 20 females Supplemental observations, as appropriate 5males and 5 females Table 2: Frequency of clinical observation and functional tests Type of observations Study duration Acute 28-day 90-day Chronic In all animals General health condition daily daily daily daily Mortality/morbidity Twice daily Twice daily Twice daily Twice daily In animals selected for functional observations Detailed clinical observations prior to first exposure within 8 hours of dosing at estimate time of peak effect at day 7 and 14 after dosing prior to first exposure once weekly thereafter prior to first exposure once during the first or second week of exposure monthly thereafter prior to first exposure once at the end of the first month of exposure every three months thereafter Functional tests prior to first exposure within 8 hours of dosing at estimate time of peak effect at day 7 and 14 after dosing prior to first exposure during the fourth week of treatment as close as possible to the end of the exposure period prior to first exposure once during the first or second week of exposure monthly thereafter prior to first exposure once at the end of the first month of exposure every three months thereafter --- Source: https://www.legislation.gov.uk/eudr/2004/73/annex/2H/division/B.43/division/4 (the official version) Page: https://openlegislation.uk/eu-directive-2004-73/annex-2H/division-B.43/division-4 Contains public sector information licensed under the Open Government Licence v3.0. Source: legislation.gov.uk, The National Archives.