Safety Evaluation of Chemicals, Relationship between Short-and Long-Term Feeding Studies in Designing an Effective Toxicity Test

Liver Hypertrophy

“…The fact that after more than 50 years of debate (Gilbert and Golberg 1965;Rowe et al 1959;Weil and McCollister 1963) the issue remains as contentious as ever prompted the European Society of Toxicologic Pathology (ESTP) to convene an expert opinion group to discuss the current state of the science. The purpose of the workshop was to discuss the significance of hepatocellular hypertrophy in rodents, define more clearly when adaptive responses become adverse, and understand the long-term consequences of hepatocellular hypertrophy in order to guide scientific opinion for risk assessment in man and dose setting for longer term animal studies.…”

Task 3 Report - PCBs in the Environment Near the Oak Ridge Reservation - A Reconstruction of Historical Doses and Health Risks

“…Worst case chemicals are those which: 1) are uniquely toxic to humans e.g., more toxic to humans than the test species, and 2) significantly more toxic to certain human subpopulations. Based upon available data (Weil and McCollister, 1963, Dourson and Starra, 1983, Lewis et al, 1990, Baird et al, 1996, the majority of chemicals do not behave in the worst-case manner assumed by regulatory agency guidelines. As a result most RfDs and MRLs represent doses that are substantially smaller then the actual dose that is protective to sensitive individuals (Baird et al, 1996;Swartout et al, 1998).…”

“…SWSAs at WAG 4 were in use from 1943to 1963(ORNL, 1987. Wastes including paper, clothing, equipment, filters, animal carcasses, and related laboratory wastes, were placed in trenches, shallow auger holes, and in piles on the ground surface to be covered at a later date.…”

Guidance Notes for Analysis and Evaluation of Repeat-Dose Toxicity Studies

“…Body weight changes (gains or losses) for individual animals and groups of animals when compared to concurrent control changes during the course of a study are a criterion of some importance (Heywood, 1981;Roubicek et al, 1964: Weil & McCollister, 1963. Such changes are usually related to food intake, and analysis of one without an analysis of the other is of limited value.…”