Clinical Pathology Changes Related to Cutaneous Irritation in the Fischer 344 Rat and New Zealand White Rabbit

Abstract An evaluation of 27 repeated dose cutaneous application studies (9 applications of 6 h over an 11-day period) indicated that several hematologic and clinical chemistry parameters may be altered by chemically induced skin irritation. Irrespective of species, values that were generally decreased included hemoglobin concentration, hematocrit, erythrocyte count, and serum concentrations of calcium, potassium, inorganic phosphorus, and creatinine. Values that were increased included the neutrophil and total leukocyte counts. Some species differences were seen; for example, while the platelet count and serum globulin concentration were increased in rabbits only, the serum glucose, sodium, and chloride concentrations were increased in rats only. The mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and serum albumin and total protein concentrations were variably affected. Changes were generally well associated with the degree of cutaneous irritation, but did not appear to be related to the chemical class of the test substances, decreased food consumption, loss of body weight, or systemic toxicity of the chemical. However, the relationship of the changes in the clinical pathology measurements to cutaneous irritation or secondary effects was not always clear. Some measurements were considered to be secondary to the cutaneous inflammation while others may be related to vascular and fluid balance alterations. Regardless of the cause of these changes, their frequent occurrence and consistent direction of change suggest a relationship to cutaneous irritation rather than systemic toxicity of the test substances. It is considered important that the interpreter of toxicologic studies be aware of these irritation-induced changes when evaluating the findings of repeated cutaneous application studies.