PHARMACOLOGY

 LOCAL TOXICITY ::

These studies are required when the new drug is proposed to be used by some special route (other than oral) in humans The drug is applied to an appropriate site like skin or vaginal mucous membrane etc to determine local effects in a suitable species Typical study designs for these studies also include three dose levels and untreated and /or vehicle control Usually 2 species are to be used and the group size should be increased with increase in duration of treatment if the drug is absorbed from the site of application appropriate systemic toxicity studies should also be carried out 

DERMAL TOXICITY STUDY ::

The study is done in rabbits and rats Daily topical (dermal) application of the test compound in its clinical dosage form should be done Test material should be applied on shaved skin covering not less than 10% of the total body surface area Porous gauze dressing should be used to hold liquid material in place Formulations with different concentrations (at least 3 ) of the test compound that are several fold higher than the clinical dosage form are used period of application may vary from 7 to 90 days depending on the intended duration of use in humans if skin irritation is grossly visible in the initial studies a recovery group should be included in the subsequent repeated dose study Local signs (erythema oedema and eschar formation ) as well as histological examination of sites of application are carried out to evaluate the results 

PHOTO-ALLERGY OR DERMAL PHOTO-TOXICITY ::

This test is done guinea pigs if the drug or a metabolise is related to an agent causing photosensitivity or the nature of action suggests such a potential (e.g. drugs is to be used in treatment of leucoderma ) Pretest in 8 animals may be done to evaluate 4 concentrations The patch is applied for 2 hours +-15 min with and without UV exposure (10 j/CM2) After 24 and 48 hours observation is done used to ascertain highest nonirritant dose Main test is performed with 10 test animals and 5 controls Induction with the dose selected from pretest is 0.3 ml /patch for 2 hour +- 15 min followed by 10 J/cm2 of UV exposure This is repeated on day 0,2,4,7,9 and 11 of the test Animals are then challenged with the same concentration of test substance between day 20 to 24 of the test with a similar 2-holur application followed by exposure to 10 j/cm2 of UV light Examination and grading of erythema and oedema formation at the sites if application of the test compound is done 24 and 48 hours after the challenge A positive control like musk ambrett or psoralin can also be used