This review investigates the incidences of decidual reactions and associated microscopic changes in Sprague-Dawley rats comparing dual-route (intravenous-IV + intraperitoneal-IP) to IV-only preclinical studies of nonimplant medical devices at Syngene International Ltd. Data from 132 rats in 14 dual-route studies and 120 rats in 12 IV-only studies were analyzed retrospectively. Sesame oil and normal saline were used as the vehicle for intraperitoneal and intravenous administration, respectively. The dual-route studies showed higher incidences of decidual reactions (9.8%) compared with IV-only studies (0.8%). Associated microscopic changes included increased mucification in the cervix (3.8% vs 0.8%) and vagina (6.1% vs 2.5%), and mammary gland hyperplasia (12.9% vs 4.2%), indicative of pseudopregnancy. The findings suggest that intraperitoneal administration of sesame oil, in presence of pseudopregnancy, significantly contributes to these effects. This review highlights the importance of understanding the potential effects of the vehicle and route of administration while interpreting the results in preclinical studies.
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