CLINICAL PATHOLOGY CHANGES RELATED TO CUTANEOUS IRRITATION IN THE FISCHER-344 RAT AND NEW-ZEALAND WHITE-RABBIT

An evaluation of 27 repeated dose cutaneous application studies (9 app lications of 6 h over an 11-day period) indicated that several hematol ogic and clinical chemistry parameters may be altered by chemically in duced skin irritation. Irrespective of species, values that were gener ally decreased included hemoglobin concentration, hematocrit, erythroc yte count, and serum concentrations of calcium, potassium, inorganic p hosphorus, and creatinine. Values that were increased included the neu trophil and total leukocyte counts. Some species differences were seen ; for example, while the platelet count and serum globulin concentrati on were increased in rabbits only, the serum glucose, sodium, and chlo ride 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 gen erally well associated with the degree of cutaneous irritation, but di d not appear to be related to the chemical class of the test substance s, decreased food consumption, loss of body weight, or systemic toxici ty of the chemical. However, the relationship of the changes in the cl inical pathology measurements to cutaneous irritation or secondary eff ects was not always clear. Some measurements were considered to be sec ondary to the cutaneous inflammation while others may be related to va scular 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 t oxicity of the test substances. It is considered important that the in terpreter of toxicologic studies be aware of these irritation-induced changes when evaluating the findings of repeated cutaneous application studies.