This position paper delineates the expert recommendations of the Regulatory Affairs Committee of the American Society for Veterinary Clinical Pathology for the use of preclinical, clinical pathology endpoints in assessment of the potential for drug-induced hepatic injury in animals and humans. Development of these guidelines has been based on current recommendations in the relevant preclinical and human clinical trial literature; they are intended to provide a method for consistent and rigorous interpretation of liver-specific data for the identification of hepatic injury in preclinical studies and potential liability for hepatic injury in human patients.

Microcytosis, hypochromasia, and l o w mean corpuscular hemoglobin are frequent hematologic abnormalities in dogs with portosystemic vascular anomalies (PSVA). The relationship of iron status t o these abnormalities is unclear. We evaluated iron status and hematologic and biochemical parameters in dogs with congenital PSVA before (25 dogs) and after (11 dogs) partial ligation of the vascular anomaly. Serum iron concentration and total iron binding capacity were subnormal in 56% and 20% of dogs with PSVA, respectively. Transferrin saturation was normal in 68%, decreased in 20%, and increased in 12% of the dogs. Plasma ferritin concentration was either normal (56%) or high (44%), and was not associated with increases in ceruloplasmin concentration. Hepatic stainable iron was increased in 10 of 16 dogs. Mean corpuscular volume (MCV), mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were decreased in more than 60% of dogs with PSVA. Serum biochemical abnormalities included high bile acid rythrocytes with a low mean cell volume (MCV), micro-E cytes (MCV < 60-63 %), occur in 33% to 72% of dogs with portosystemic vascular anomalies (PSVA).'~4 Hypochromasia and low mean corpuscular hemoglobin concentration (MCHC) occur in 4% to 100% of dogs with PSVA. I-' Although the cause of these hematologic abnormalities is unclear, the frequent association of microcytosis, hypochromasia, and low mean corpuscular hemoglobin (MCH) with iron suggests that their occurrence with PSVA may be related to a decrease in iron availability. The results of preliminary studies of the direct assessment of iron status in dogs with congenital PSVA detail microcytosis in association with decreased serum iron concentrations, and normal or decreased total iron binding capacity (TIBC).4,7.X Body iron stores, estimated by measuring ferritin7 or hepatic hemosiderin4 were normal or increased, suggesting a problem in iron utilization rather than an absolute iron deficiency.'.'" Further evidence of abnormal iron metabolism in dogs with PSVA is provided by the development of microcytosis, hypochromasia, low serum iron, and decreased TIBC, and an increased hepatic iron content after surgical creation of a portosystemic shunt." These studies have shown that iron status is abnormal in dogs with PSVA; however, the pathogenesis of these abnormalities and their relationship to microcytosis remains unclear. The objectives of this study were, therefore, to define further the relationship of iron status to erythrocyte volume in dogs with congenital PSVA, and to correlate the effects of congenital PSVA on iron status, hematologic and clinical biochemical indices by comparing these measurements before and after surgical correction of the shunts. Materials and Methods DogsTwenty-five dogs with congenital PSVA referred to the Queen Mother Hospital, Royal Veterinary College between 1992 and 1994 were entered in this study. A diagnosis of PSVA was suspected on the basis of compatible clinical signs and clinicopathologic findings.12~" Ultrasonograp...

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The purpose of this paper by the Regulatory Affairs Committee (RAC) of the American Society for Veterinary Clinical Pathology (ASVCP) is to review the current regulatory guidances (eg, guidelines) and published recommendations for best practices in veterinary toxicologic clinical pathology, particularly in the pharmaceutical and biotechnology industries, and to utilize the combined experience of ASVCP RAC to provide updated recommendations. Discussion points include (1) instrumentation, validation, and sample collection, (2) routine laboratory variables, (3) cytologic laboratory variables, (4) data interpretation and reporting (including peer review, reference intervals and statistics), and (5) roles and responsibilities of clinical pathologists and laboratory personnel. Revision and improvement of current practices should be in alignment with evolving regulatory guidance documents, new technology, and expanding understanding and utility of clinical pathology. These recommendations provide a contemporary guide for the refinement of veterinary toxicologic clinical pathology best practices.