Common use of ASA Clause in Contracts

ASA. The studies refered to include long term administration to rats and ferrets and carcinogenicity studies in the mouse and rat. Notwithstanding the above, a programme of toxicological evaluation of balsalazide has been designed to fulfil the present day requirements of the major Regulatory Agencies World Wide. This programme includes re-evaluation of the consequences of repeated administration to rodents and non-rodents, reproduction toxicology and necessary toxicokinetics to enable overall evaluation. To date the initial findings in preliminary studies using high doses of balslazide at large multiples of the proposed dose for man, are substantiating the balsalazide has a low order of toxicity. /s/ ▇▇▇▇▇ ▇▇▇▇▇ ▇▇▇▇▇ ▇.▇▇▇▇▇. Dated: 31st. August, 1992. -------------------------------------------------------------------------------- ADVISOR ON TOXICOLOGY AND SAFETY EVALUATION (R&D Schedule 2 cont ...) COLAZIDE (R) DEVELOPMENT - COMPLETED STUDIES AND ADDITIONAL WORK ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------------- Glycyx Completed ------------------------ EC Registration Dossier Headings by Biorex Repeat/New Reconstruct ---------------------------------------------------------------------------------------------------------- ----------------------------------- PART IIIA SINGLE DOSE TOXICITY ----------------------------------- - Mouse, oral . - Mouse, ip . - Rat, oral . * - Rat, ip (iv) . * - Mouse, oral: 4-ABA . - Rat, oral: 4-ABA . - Mouse, oral: 5-ASA . - Rat, oral: 5-ASA . - Mouse, oral: 5-ASA/4-ABA . - Rat, oral: 5-ASA/4-ABA . - Mouse, oral: BSZ impurity . - Mouse, ip: BSZ impurity . - Mouse, ip: Colazide . ----------------------------------- PART IIIB - REPEATED DOSE TOXICITY ----------------------------------- Max. Tolerated Dose ------------------- - Dog . Subacute -------- - Rat, 14 days, oral . . * - Mouse, 7 days, oral: BSZ . * - Mouse, 28 day, oral BSZ . * - Rat, 7 days, oral: BSZ . * - Rat, 28 day, oral: BSZ . * - Dog, 28 days, oral . Chronic ------- - Rat, 96 week, oral . . - Ferret, 26 week, oral . . - Dog, 26 week, gavage . - Rat 26 week, gavage . ----------------------------------- PART IIIC Reproduction Studies -----------------------------------