Proposed new classification scheme for chemical injury to the human eye.

PURPOSE: Various ocular alkali burn classification schemes have been published and used to grade human chemical eye injuries for the purpose of identifying treatments and forecasting outcomes. The ILSI chemical eye injury classification scheme was developed for the additional purpose of collecting detailed human eye injury data to provide information on the mechanisms associated with chemical eye injuries. This information will have clinical application, as well as use in the development and validation of new methods to assess ocular toxicity. METHODS: A panel of ophthalmic researchers proposed the new classification scheme based upon current knowledge of the mechanisms of eye injury, and their collective clinical and research experience. Additional ophthalmologists and researchers were surveyed to critique the scheme. The draft scheme was revised, and the proposed scheme represents the best consensus from at least 23 physicians and scientists. RESULTS: The new scheme classifies chemical eye injury into five categories based on clinical signs, symptoms, and expected outcomes. Diagnostic classification is based primarily on two clinical endpoints: (1) the extent (area) of injury at the limbus, and (2) the degree of injury (area and depth) to the cornea. CONCLUSIONS: The new classification scheme provides a uniform system for scoring eye injury across chemical classes, and provides enough detail for the clinician to collect data that will be relevant to identifying the mechanisms of ocular injury.

Tiered testing strategies--acute local toxicity.

More work has been done to develop alternatives to animal use in the areas of eye and skin irritation than in any area other than carcinogenicity. There has long been a belief both in the scientific community and among the public that the development of nonanimal tests in these areas should be simple and straightforward. After more than 20 yr of research, we can identify materials corrosive to the skin without using animals, but the assessment of irritation using in vitro methods alone is still an illusive goal. This review of current recommendations and industry practices that reduce the number of animals needed for these two tests concludes that animal use for skin irritation testing is not necessary today, with currently available and accepted methodology, except for regulatory reasons. Scientifically sound improvements in current eye irritation methods are also available. Advances in the understanding of the mechanisms of eye irritation that have been made in the last 5 yr should lead to improved in vitro methods for this endpoint. In the meantime, changes should be made in the current animal protocol to reduce pain and distress. This paper provides an overview of the progress that has been made toward discontinuing the use of animals in tests to determine the potential of materials to cause skin or eye damage after a single acute exposure. It also discusses some additional changes that could be made now to reduce animal use further or to reduce pain and distress in the testing that must still be done until such time as we can meet the ultimate goal--validated and accepted nonanimal methods for these endpoints.

Hematology analyzer comparison: Ortho ELT-8/ds vs. Baker 9000 for healthy dogs, mice,and rats.

A Baker 9000 hematology analyzer (electronic impedance) was purchased to replace an Ortho ELT-8/ds analyzer (laser optics) due to discontinued technical support. An analytical comparison of hemograms from healthy dogs, rats, and mice was made from paired disodium ethylenediamine tetra-acetate anticoagulated blood samples. Both instruments were calibrated with human blood products, and the ELT-8/ds hematocrit (HCT) was calibrated to a spun packed cell volume (PCV) for each species. For Beagle dogs (n = 49), Baker 9000 mean platelet (PCV) counts had a negative bias of -89 X 10(3)/microliter when compared to ELT-8/ds values. Mean +/- standard error manual PLT counts compared well with Baker 9OOO values for dogs (n = 10): 369 +/- 28 vs. 367 +/- 27 X 10(3)/microliter; r = 0.93. For CD-1 mice (n = 44), Baker 9000 mean white blood cell (WBC) counts had positive biases of 1. 1 X 10(3)/microliter when compared to ELT-8/ds and 0.5 X 10(3)/microliter when compared to hemacytometer counts. Diluted microsamples using the predilution mode on the Baker 9000 compared well with undiluted samples for mice. For Sprague-Dawley rats (n = 70), Baker 9000 mean WBC, red blood cell (RBC), and PLT counts had absolute biases of 0.8 X 10(3)/microliter, -1.09 X 10(6)/microliter, and -357 X 10(3)/microliter, respectively, when compared to ELT-8/ds values. Baker 9000 RBC, WBC, and PLT counts from rats compared well with reference hemacytometer counts. The Baker 9000 HCT determination for rats had an absolute negative bias of 6% when compared to the ELT-8/ds values or spun PCV. The Baker 9000 required whole blood calibration to PCV for accurate determination of HCT for rats. The biases between analyzers may be due to inherent physical differences between the analytical methods and/or the calibration techniques.