Pivotal Study to Demonstrate the Safety of Estradiol Administered in Feed to American Eels (Anguilla rostrata), Protocol No. NE-003

Novaeel, Inc., Halifax NS

Investigators

Abstract

RESEARH & RELATED Other Project Information: Section 7 Project Summary/Abstract This pivotal target animal safety study is required by the FDA Center for Veterinary Medicine to complete the target animal safety technical section of the new animal drug application (Guidance for Industry 185, Target Animal Safety Studies for Veterinary Pharmaceutical Products). This study is to demonstrate the margin of safety when estradiol is administered in feed (5 ppm) to American eels (Anguilla rostrata). Estradiol will be incorporated into Type A Medicated Article at the rate of 0.1%. The premix will be top-coated onto the fish feed. Eels will be fed to satiation daily throughout the treatment period starting with wild-caught glass eels that weigh 0.2 to 0.5 g each. The study will consist of 12 experimental units in 4 treatment groups, 3 experimental units will be randomly allocated to each treatment group. The treatment groups are: 0X (no estradiol), 1X (5 ppm), 3X (15 ppm) or 5X (25 ppm) for 315 days. Each experimental unit will initially consist of 300 glass eels stocked into 1 tank. Eels will be weighed at 35-day intervals and as they grow eel stocking density will be maintained at optimal levels by a) adding more water into the tank, b) splitting eel numbers into an additional tank(s), c) grading so that eels of similar sizes are housed together. A maximum of 4 tanks will be assigned to each experimental unit. All eels will be euthanized and subjected to gross external examination after 315 days. Ten randomly selected eels from each tank will be necropsied and protocol-specified tissues examined. Two eels will be randomly selected from those necropsied in each group and specified tissues will be evaluated by histopathological examination. Findings will be statistically analyzed. Preliminary experiments have shown that continuous administration of estradiol- medicated feed is necessary to produce market weight eels in a commercially feasible period of less than one year and no adverse effects on eels were observed.