3 In the Drugs and Cosmetics Rules, 1945 - amam-ayurveda.org

31One male and one female from each litter of F 1 generation (total 15 males and 15 females ineach group) should be selected at weaning and treated with vehicle or test substance (at thedose levels described above) throughout their periods of growth to sexual maturity, pairing,gestation, parturition and lactation. Mating performance and fertility of F 1 generation shouldthus be evaluated to obtain the F 2 generation whose growth parameters should be monitoredtill weaning. The criteria of evaluation should be the same as described earlier (3.4.1).Animals should be sacrificed at the end of the study and the observation parameters shouldinclude (Dams) body weight, food intake, general signs of intoxication, progress of gestation/parturition periods and gross pathology (if any); and for pups, the clinical signs, sex-wisedistribution in dose groups, body weight, growth parameters, gross examination, survival andautopsy (if needed) and where necessary, histopathology.1.4 1.4 Local toxicityThese studies (see Appendix I, item 4.5) are required when the new drug is proposed to beused by some special route (other than oral) in humans. The drug should be applied to anappropriate site (e.g., skin or vaginal mucous membrane) to determine local effects in asuitable species. Typical study designs for these studies should include three dose levels anduntreated and/ or vehicle control, preferably use of 2 species, and increasing group size withincrease in duration of treatment. Where dosing is restricted due to anatomical or humanereasons, or the drug concentration cannot be increased beyond a certain level due to theproblems of solubility, pH or tonicity, a clear statement to this effect should be given. If thedrug is absorbed from the site of application, appropriate systemic toxicity studies will also berequired.Notes:(i) (i) Dermal toxicity study: The study should be done in rabbit and rat. Dailytopical (dermal) application of test substance in its clinical dosage form shouldbe done. Test material should be applied on shaved skin covering not lessthan 10% of the total body surface area. Porous gauze dressing should beused to hold liquid material in place. Formulations with different