RESUMEN

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.

RESUMEN

In 1980 and 1981 Mennonite descendants of a group of Russian immigrants participated in a multidisciplinary study of biological aging. The Mennonites live in Goessel, Kansas, and Henderson, Nebraska. In 1991 the survival status of the participants was documented by each church secretary. Data are available for 1009 individuals, 177 of whom are now deceased. They ranged from 20 to 95 years in age when the data were collected. Biological ages were computed using a stepwise multiple regression procedure based on 38 variables previously identified as being related to survival, with chronological age as the dependent variable. Standardized residuals place participants in either a predicted-younger or a predicted-older group. The independence of the variables biological age and survival status is tested with the chi-square statistic. The significance of biological age differences between surviving and deceased Mennonites is determined by t test values. The two statistics provide consistent results. Predicted age group classification and survival status are related. The group of deceased participants is generally predicted to be older than the group of surviving participants, although neither statistic is significant for all subgroups of Mennonites. In most cases, however, individuals in the predicted-older groups are at a relatively higher risk of dying compared with those in the predicted-younger groups, although the increased risk is not always significant.

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RESUMEN

Hostility-related variables have been categorized as to kinds of emotions, attitudes, and behaviors. Relatively few studies have explored whether genetic factors contribute to individual differences in these variables. Moreover, the majority of this research has involved male subjects. The present study utilized the twin method to evaluate the influence of genetic factors on hostility-related emotions, namely, trait anger and irritability, hostility-related attitudes, namely cynical hostility and suspiciousness, and hostility-related behaviors, namely, physical, verbal, and indirect aggression in adult women. Responses on the measure of trait anger showed evidence of significant heritability. However, evidence for a genetic component to responses on the irritability scale was less clear. There was no support for the notion of a genetic component to the measure of suspiciousness, and the evidence of a genetic contribution for cynical hostility was not significant. It was expected that due to environmental influences for women, only certain forms of aggression would show genetic variance, namely, verbal and indirect as opposed to physical forms. The results were generally congruent with these expectations.

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RESUMEN

Five alternative techniques, each of which had been successfully used by one of the participating companies, were evaluated in the assessment of the eye-irritation potential of 32 samples. The 32 samples included chemical ingredients and preparations from household cleaning product, personal care, and cosmetic categories. Historical data from rabbit eye irritation tests in vivo existed for each sample; it was therefore not necessary to carry out any tests in vivo as part of this evaluation exercise. The five alternative methods used were the silicon microphysiometer test, the Microtox test, the neutral red uptake assay, the chorioallantoic membrane vascular assay (CAMVA) and the hen egg test-chorioallantoic membrane assay (HETCAM). Three of the assays were conducted in two laboratories, allowing an interlaboratory comparison of performance to be made. The CAMVA assay was carried out on 10-day-old as well as on 14-day-old fertile eggs. Correlations between the data sets in vivo and in vitro were determined for the five assays. The results demonstrated that for the materials tested, all of the assays show some promise as alternative methods to the rabbit eye test in vivo in the prediction of eye irritation, and that the reproducibility of results of those techniques carried out in two laboratories was very good. The results from 14-day and 10-day CAMVA assays were virtually identical. It is recommended that a larger-scale validation exercise be carried out to demonstrate the ultimate usefulness of these alternative procedures in the safety evaluation process.

RESUMEN

Synopsis Experience in a large manufacturing unit showed that splashes of undiluted shampoo only produced transient effects in the eyes of production and packaging staff; over the same period, very few complaints of eye irritation were received from shampoo users, none of which were of a serious nature. Predictive testing is needed to make sure that new formulations are not severe eye irritants though rabbit eye testing may tend to exaggerate the likely human response. Detergent concentration is the principal factor influencing findings in the rabbit eye and an active matter content of 2.5-3.0% (usually representing a 20% aqueous dilution of shampoo) gives the best discrimination between formulations whilst producing no signs of distress in the animals; for typical anionic shampoos, testing at this concentration is recommended, without subsequent rinsing. Rabbit eye tests should never be conducted at higher concentrations until their innocuousness at 20% dilution has been shown and, even then, stronger preparations should only be instilled if they contain new ingredients for which the potential risk in human use are unknown. Conduct of all rabbit eye testing as a comparison with a 'control' formulation of equivalent concentration, known to be well tolerated under market conditions, is recommended. For preliminary screening, an in vitro test using freshly-isolated buccal mucosa cells from human volunteers may be useful, irritancy being assessed by the proportion of cells showing loss of visible nuclei when examined by phase-contrast microscopy.

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