A summary report of the COLIPA international validation study on alternatives to the draize rabbit eye irritation test.

The principal goal of this study was to determine whether the results from a set of selected currently available alternative methods as used by cosmetics companies are valid for predicting the eye irritation potential of cosmetics formulations and ingredients and, as a consequence, could be valid replacements for the Draize eye irritation test. For the first time in a validation study, prediction models (PMs) that convert the in vitro data from an assay to a prediction of eye irritation were developed for each alternative method before the study began. The PM is an unequivocal description of the relationship between the in vitro and the in vivo data and allows an objective assessment of the reliability and relevance of the alternative methods. In this study, 10 alternative methods were evaluated using 55 test substances selected as representative of substances commonly used in the cosmetics industry (23 ingredients and 32 formulations). Twenty of the single ingredients were common to the European Commission/British Home Office (EC/HO) eye irritation validation study (Balls et al., 1995b). The test substances were coded and supplied to the participating laboratories. The results were collected centrally and analysed independently, using statistical methods that had been agreed before the testing phase began. Each alternative method was then evaluated for reliability and relevance in assessing eye irritation potential. Using the criteria of both reliability and relevance as defined in the study, the preliminary results indicate that none of the alternative methods evaluated could be confirmed as a valid replacement for the Draize eye irritation test across the full irritation scale. However, three alternative methods-the fluorescein leakage test, the red blood cell assay (classification model) and the tissue equivalent assay-each satisfied one criterion of reliability or relevance. Further investigation of the decoded data from this study to explore more fully the relationship between the in vitro data and the in vivo data is recommended. Such a review may allow the development of new prediction models to be tested in a subsequent validation study.

Physical performance decrements in children with sickle cell anemia.

Prior studies have suggested that cardiorespiratory dysfunction might contribute to the inability of children with sickle cell anemia to exercise competitively with normal children. This article presents a study designed to detect differences in performance of routine physical activities between groups of children having homozygous hemoglobin of sickle cell anemia (HbSS) and those with normal hemoglobin (HbAA). Thirty 10-year-old girls were divided into two equal groups exhibiting no significant differences in height, weight, or body surface area. Each subject performed 20-yd swimming, 40-yd swimming, and 100-yd "potato" foot-racing activities. Results showed significant performance decrements in HbSS compared with HbAA children. Performance decrements on the 20-yd swimming were found to be significantly greater than in either the 40-yd swimming or the 100-yd "potato" races. Assessment of 20-yd swim time as a fraction of 40-yd swim time showed diminished capacity of HbSS children for "burst activity." It is concluded that distance might play a role in the capacity of HbSS children to compete with HbAA children in racing activities such as those encountered in school-based physical education programs. Parents and educators should consider that short distance racing might exaggerate the inability of children with sickle cell anemia to compete with normal children.

Amelioration of nephrotoxicity associated with synthetic oxygen transport media.

Use of synthetic oxygen transport media offers the potential advantages of reducing requirements for coadministration of blood products and oxygen at the scene of mass casualty situations. Previous studies have shown perfusions of isolated kidneys with stroma-free hemoglobin (SFH) to be physiological while those with Fluosol-DA (20% FDA) have been associated with low glomerular filtration rate, urinary flow rate, and fractional reabsorption of sodium and potassium (FrNa+ and FrK+). In the present studies, perfusions with SFH/FDA mixtures showed normal glomerular filtration rate, a 50% lower urinary flow rate, and FrNa+ values 3% to 5% higher than SFH controls. Compared with 20% FDA perfusions, nephrotoxic effects of SFH/FDA combinations were moderate. Compared with SFH/FDA mixtures, perfusion with 20% FDA showed lower urinary flow and glomerular filtration rates. Ultrastructural assessment of glomerular filter revealed that FDA emulsion particles were adherent to epithelial podocytes. We conclude that resuscitation with a mixture of SFH and FDA may ameliorate the previously reported nephrotoxicity associated with the use of FDA alone.

Assessment of growth problems in adolescents.

Investigation of an adolescent growth problem consists of taking an adequate history and doing a complete physical examination. This procedure, along with a calculation of bone age and height/weight age, will allow family physicians to decide on the cause of the growth variance in most patients. Relatively simple studies can be done in the family physician's office to delineate the major causes of growth problems; the majority will be unrelated to the endocrine system. Further studies may be needed in a hospital-based setting.