Four Week Toxicity Study of WR279396 After Daily Dermal Application in CD (registered trademark) Rats
Abstract
This study evaluated the toxicity of WR279396 (Iowa Formulation 232 containing 15% paromomycin sulfate and 0.5% gentamicin sulfate) in CD* rats following four weeks of daily dermal application. Three groups, each composed of 10 rats/sex, were initially given the test article twice daily by dermal application for the first five days. The volume of WR279396 administered per application (2 applications/day) were 0.07, 0.33, and 1.67 ml/kg, respectively, in low, mid and high dose animals. This corresponds to doses of 20, 100 and 500 mg/kg/day of paromomycin + 0.7, 3.3, 16.7 mg/kg/day of gentamicin, respectively. A control group of 10 male and 10 female rats received the test article vehicle (WR279396-Placebo, Iowa Formulation 232) by dermal application at a dosing volume of 1.67 ml/kg per application. Due to the appearance of moderate to severe erythema in mid and high dose animals on days 4 and 5, the volume (amount) of test article or vehicle control article administered was reduced to one-half the initial dose levels beginning on day 6 and for the remainder of the study. On day 6 and thereafter, test article volume (amount) was administered once daily instead of as a split dose twice daily. Following reduction in dosing frequency, very slight erythema (draize score = 1, barely perceptible), not accompanied by edema formation, was seen in most high dose animals. Acanthosis, thickening of the stratum spinosum layer of the epidermis, was also observed in several high dose animals and was generally of minimal severity. Except for one mid dose male, these dermal histologic changes were not seen at lower dosing volumes of WR279396, i.e. 0.33 or 0.07 ml/kg/day. Clinical signs, body weights, food intake, clinical chemistry and hematology parameters, ophthalmology evaluations and organ weights were not affected by test article treatment in any of the dose levels tested.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 24, 1995
- Accession Number
- ADA573993
Entities
People
- Barry S. Levine
Organizations
- University of Illinois at Chicago