The Notification of New Substances Regulations 1993

Toxicological studies

Fertility studies (one species, one generation, male and female, most appropriate route of administration).

If there are equivocal findings in the first generation, study of a second generation is required.

Depending upon the dosing schedule it may be possible in this study to obtain an indication of teratogenicity. A positive indication should be examined in a formal teratology study.

• Teratology study (one species, most appropriate route of administration).

• This study is required if teratogenicity has not been examined in the fertility study.

• Sub-chronic and/or chronic toxicity study, including special studies (one species, male and female, most appropriate route of administration) shall be required if the results of the repeated-dose study in Annex VII or other relevant information demonstrate the need for further appropriate investigation.

• The effects which would indicate the need for such a study could include for example:

  (a)

  serious or irreversible lesions;

  (b)

  a very low or absence of a “no effect” level;

  (c)

  a clear relationship in chemical structure between the substance being studied and other substances which have been proved dangerous.

• Additional mutagenesis studies and/or screening study(ies) for carcinogenesis as prescribed in the testing strategy described in Annex V.When both tests in the base set are negative, further tests shall be conducted according to the specific properties and the proposed use of the substance.

• When a test or both tests were positive in the base set, a supplementary should include the same or different end points in other in vivo test methods.

• Basic toxicokinetic information.