{
  "url": "https://openlegislation.uk/eu-directive-2004-73/annex-2H/division-B.43/division-4",
  "json_url": "https://openlegislation.uk/eu-directive-2004-73/annex-2H/division-B.43/division-4.json",
  "legislation": "eudr/2004/73",
  "legislation_title": "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)",
  "legislation_url": "https://openlegislation.uk/eu-directive-2004-73",
  "path": "annex/2H/division/B.43/division/4",
  "kind": "division",
  "number": "4",
  "heading": "REFERENCES",
  "text": "Table 1:\nMinimum numbers of animals needed per group when the neurotoxicity study is conducted separately or in combination whit studies\nIncludes five animals selected for functional testing and detailed clinical observations as part of the neurotoxicity study\nNEUROTOXICITY STUDY CONDUCTED AS:\nSeparate study\nCombined study with the 28-day study\nCombined study with the 90-day study\nCombined study with the chronic toxicity study\nTotal number of animals per group\n10males and 10 females\n10males and 10 females\n15males and 15 females\n25males and 25 females\nNumber of animals selected for functional testing including detailed clinical observations\n10males and 10 females\n10males and 10 females\n10males and 10 females\n10males and 10 females\nNumber of animals selected per perfusion in situ and neurohistopathology\n5males and 5 females\n5males and 5 females\n5males and 5 females\n5males and 5 females\nNumber of animals selected for repeated dose/subchronic/chronic toxicity observations, haematology, clinical biochemistry, histopathology, etc. as indicate in the respective Guidelines\n5males and 5 females\n10males and 10 females\n20malesand 20 females\nSupplemental observations, as appropriate\n5males and 5 females\nTable 2:\nFrequency of clinical observation and functional tests\nType of observations\nStudy duration\nAcute\n28-day\n90-day\nChronic\nIn all animals\nGeneral health condition\ndaily\ndaily\ndaily\ndaily\nMortality/morbidity\nTwice daily\nTwice daily\nTwice daily\nTwice daily\nIn animals selected for functional observations\nDetailed clinical observations\nprior to first exposure\nwithin 8 hours of dosing at estimate time of peak effect\nat day 7 and 14 after dosing\nprior to first exposure\nonce weekly thereafter\nprior to first exposure\nonce during the first or second week of exposure\nmonthly thereafter\nprior to first exposure\nonce at the end of the first month of exposure\nevery three months thereafter\nFunctional tests\nprior to first exposure\nwithin 8 hours of dosing at estimate time of peak effect\nat day 7 and 14 after dosing\nprior to first exposure\nduring the fourth week of treatment as close as possible to the end of the exposure period\nprior to first exposure\nonce during the first or second week of exposure\nmonthly thereafter\nprior to first exposure\nonce at the end of the first month of exposure\nevery three months thereafter",
  "extent": "E+W+S+N.I.",
  "status": null,
  "version": "current",
  "annotations": [
    {
      "type": "footnote",
      "label": "f1",
      "text": "Includes five animals selected for functional testing and detailed clinical observations as part of the neurotoxicity study"
    }
  ],
  "outstanding_effects": [],
  "provenance": {
    "source": "legislation.gov.uk",
    "source_url": "https://www.legislation.gov.uk/eudr/2004/73/annex/2H/division/B.43/division/4",
    "retrieved_at": "2026-11-01T15:22:47.605967+00:00"
  },
  "licence": "Open Government Licence v3.0",
  "licence_url": "https://www.nationalarchives.gov.uk/doc/open-government-licence/version/3/",
  "attribution": "Contains public sector information licensed under the Open Government Licence v3.0. Source: legislation.gov.uk, The National Archives."
}