Daily 6-hour restraint decreases Sprague Dawley® rat body weight gain in subchronic toxicity studies

ACT 2023 -- Safety assessment of pharmaceuticals and chemicals with potential for repeated human exposure involves determining toxicity in studies that align with country-specific regulatory frameworks. A minimum 13-week study is required to support Phase II or III clinical trials, and a 13-week study following Organisation for Economic Co-operation and Development (OECD) guidelines is required for chemicals depending on the tonnage band (OECD 408 for oral ingestion risk or OECD 413 for inhalation risk). Exposure duration for inhaled therapeutics depends on clinical safety margins, while rodent exposure in compliance with the OECD 413 guideline is 6 hours/day for 5 days/week. For orally consumed pharmaceuticals and chemicals, rodent administration is daily and only requires a few minutes handling per animal. A comparison of 13-week toxicity studies with different dose routes using Crl:CD®(SD) rats was conducted to assess the impact of restraint on body weight as a health assessment. Data were averaged from the control groups of recent studies for daily oral gavage and 6 hours/5-7 days/week inhalation dosing scenarios (9 and 6 studies, respectively).