Scientific and Regulatory Policy Committee Points to Consider: Integration of Clinical Pathology Data With Anatomic Pathology Data in Nonclinical Toxicology Studies

Abstract

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Comparative Impact of Various Fasting Periods on the Welfare of Sprague-Dawley Rats With or Without Supplementation

“…Generally, decreases in ALP are often considered clinically insignificant and in rodents ALP is not a useful marker of biliary injury or cholestasis because the intestinal isoenzyme is the main source of serum ALP activity. 34 While increases in ALP are primarily indicative of gastrointestinal (GI) injury in rodents, decreases in ALP may also be suggestive of reduced GI activity due to fasting as observed in this study and previous reports. 4,19,21,29,38,39 Moreover, the prevention of ALP decreases in the 16-hour DG group may support this notion.…”

A Commentary on Fasting of Nonclinical Research Animals

“…Additional tests may be included in study protocols to help characterize the mechanism of test article action, to assist in prioritization of candidate molecules, or to address requests by regulatory authorities; these ancillary tests include acute phase proteins, hormones, and exploratory and established biomarkers of renal, hepatic, cardiac, and vascular injury. 33,34 In cases of protocol-driven clinical pathology blood collections that are required by both the European Union and United States Good Laboratory Practice Guidelines for nonclinical research. The same standardized protocols under the jurisdiction of the Norwegian Animal Research Authority have been put under extreme limits on the sudden fasting (acute food deprivation) of laboratory rodents that are accustomed to the ad libitum access to food.…”

“…Clinical chemistry data supports the conclusion that the standard fasting of 12-to 16-hour duration is a benign or "good" stress (eustress) that is brief in duration and is amenable to correction by normal homeostatic mechanisms. 33,34 Under current regulatory guidelines that define stress and distress anthropomorphically, based on the fact the humans often report enhanced mood and positive subjective experiences with fasting, then animals subjected to intermittent fasting in research laboratories worldwide cannot be presumed to exist in a negative emotional state. What is done in nonclinical research laboratories around the globe is to administer novel compounds at novel doses to living organisms to test for safety and efficacy.…”

“…Additional tests may be included in study protocols to help characterize the mechanism of test article action, to assist in prioritization of candidate molecules, or to address requests by regulatory authorities; these ancillary tests include acute phase proteins, hormones, and exploratory and established biomarkers of renal, hepatic, cardiac, and vascular injury. 33,34…”

“…Clinical chemistry data supports the conclusion that the standard fasting of 12- to 16-hour duration is a benign or “good” stress (eustress) that is brief in duration and is amenable to correction by normal homeostatic mechanisms. 33,34…”