Exposure data for cosmetic products: facial cleanser, hair conditioner, and eye shadow.

Reliable exposure information for cosmetic and other personal care products and ingredients is needed in order to conduct safety assessments. Essential information includes both the amount of product applied, and the frequency of use. To obtain current data, a study to assess consumer use practices was undertaken. Three widely used types of cosmetic products - facial cleanser, hair conditioner, and eye shadow - were included in the study. Three hundred and sixty women, ages 18-69 years, who regularly use the products of interest, were recruited nationwide within the US. Subjects were provided with a new container of the brand of product they normally use and kept diaries and recorded detailed daily usage information over a two week period. Products were weighed at the start and completion of the study in order to determine the total amount of product used. Statistical analyses of the data were conducted to derive summary distributions of use patterns. The mean and median usage per application, respectively, for the three product types were: facial cleanser, 2.57 g and 2.11 g; hair conditioner, 13.13 g and 10.21 g; and eye shadow, 0.03 g and 0.009 g. The mean and median usage per day for the three product types was: facial cleanser, 4.06 g and 3.25 g; hair conditioner, 13.77 g and 10.62 g; and eye shadow, 0.04 g and 0.010 g. The mean number of applications per day for facial cleanser, hair conditioner, and eye shadow was 1.6, 1.1, and 1.2, respectively. This study provides an estimate of current exposure information for commonly used products which will be useful for risk assessment purposes.

Exposure data for cosmetic products: lipstick, body lotion, and face cream.

Accurate exposure information for cosmetic products and ingredients is needed in order to conduct safety assessments. Essential information includes both the amount of cosmetic product applied, and the frequency of use. To obtain current data, a study to assess consumer use practices was undertaken. The study included three widely used cosmetic product types: lipstick, body lotion, and face cream. Three hundred and sixty women, ages 19-65 years, who regularly use the products of interest, were recruited at ten different geographical locations within the US. The number of recruits was chosen to ensure a minimum of 300 completes per product type. Subjects were provided with prototype test products, and kept diaries and recorded detailed daily usage information over a two week period. Products were weighed at the start and completion of the study in order to determine the total amount of product used. Statistical analysis of the data was conducted to derive summary distribution of use patterns. The mean and median usage per application, respectively, for the three products was: face cream, 1.22 g and 0.84 g; lipstick, 10 mg and 5 mg; and body lotion, 4.42 g and 3.45 g. The mean and median usage per day for the three products was: face cream, 2.05 g and 1.53 g; lipstick, 24 mg and 13 mg; and body lotion, 8.70 g and 7.63 g. The mean number of applications per day for face cream and lipstick was 1.77 and 2.35, respectively. For body lotion, the mean number of applications per day was dependent on body area, and was 2.12, 1.52, 1.11, 0.95, 0.43, 0.26, and 0.40 for hands, arms, legs, feet, neck and throat, back, and other body areas, respectively. The effect of product preference on use practices was also investigated. This study provides current cosmetic exposure information for commonly used products which will be useful for risk assessment purposes.

Subchronic inhalation studies of complex fragrance mixtures in rats and hamsters.

Users of consumer products are invariably and intentionally exposed to complex mixtures in such products. With finished fragrance products, these mixtures may represent 100 or more fragrance raw materials (FRMs). The objective of the described studies was to evaluate the safety of finished fragrance products via the inhalation route. In total, the finished products contained approximately 100 FRMs at concentrations of 1% or greater. Major FRMs evaluated included benzyl acetate, coumarin, hydroxycitronellal, musk ketone, 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta-gamma-2-be nzopyran (HHCB) and phenyl ethyl alcohol. Groups of rats or hamsters were exposed by inhalation (whole body) to the mixtures at 5, 9 or 50 mg/m3 for 4 h per day, 5 days per week for 6 or 13 weeks. For each of the fragrance products, the doses used generally represented a ten- to 100-fold exaggeration of levels expected to be achieved during typical use by consumers. With one exception, the fragrances were aerosolized prior to introduction into the inhalation chamber. The exception product was formulated with a propellant, packaged in a pressurized container and expelled with an automated actuator. In all studies, chamber concentrations of fragrance were monitored. Particle sizes ranged from 0.5 to 7.5 microm, depending on the study. Subchronic exposure to all fragrance mixtures resulted in no toxicologically significant effects on animal survival, behavior, body weights or weight gains, organ weights, or in hematology, clinical chemistry, or urinalysis parameters. No gross pathological or histopathological findings related to test material exposures were observed. These studies support the conclusions that the fragrance mixtures would not pose a hazard to product users based on repeated and exaggerated inhalation exposures of animals.

The CTFA Evaluation of Alternatives Program: an evaluation of in vitro alternatives to the Draize primary eye irritation test. (Phase III) surfactant-based formulations.

The CTFA Evaluation of Alternatives Program is an evaluation of the relationship between data from the Draize primary eye irritation test and comparable data from a selection of promising in vitro eye irritation tests. In Phase III, data from the Draize test and 41 in vitro endpoints on 25 representative surfactant-based personal care formulations were compared. As in Phase I and Phase II, regression modelling of the relationship between maximum average Draize score (MAS) and in vitro endpoint was the primary approach adopted for evaluating in vitro assay performance. The degree of confidence in prediction of MAS for a given in vitro endpoint is quantified in terms of the relative widths of prediction intervals constructed about the fitted regression curve. Prediction intervals reflect not only the error attributed to the model but also the material-specific components of variation in both the Draize and the in vitro assays. Among the in vitro assays selected for regression modeling in Phase III, the relationship between MAS and in vitro score was relatively well defined. The prediction bounds on MAS were most narrow for materials at the lower or upper end of the effective irritation range (MAS = 0-45), where variability in MAS was smallest. This, the confidence with which the MAS of surfactant-based formulations is predicted is greatest when MAS approaches zero or when MAS approaches 45 (no comment is made on prediction of MAS > 45 since extrapolation beyond the range of observed data is not possible). No single in vitro endpoint was found to exhibit relative superiority with regard to prediction of MAS. Variability associated with Draize test outcome (e.g. in MAS values) must be considered in any future comparisons of in vivo and in vitro test results if the purpose is to predict in vivo response using in vitro data.

Framework for validation and implementation of in vitro toxicity tests.

The development and application of in vitro alternatives designed to reduce or replace the use of animals, or to lessen the distress and discomfort of laboratory animals, is a rapidly developing trend in toxicology. However, at present there is no formal administrative process to organize, coordinate, or evaluate validation activities. A framework capable of fostering the validation of new methods is essential for the effective transfer of new technologic developments from the research laboratory into practical use. This committee has identified four essential validation resources: chemical bank(s), cell and tissue banks, a data bank, and reference laboratories. The creation of a Scientific Advisory Board composed of experts in the various aspects and endpoints of toxicity testing, and representing the academic, industrial, and regulatory communities, is recommended. Test validation acceptance is contingent on broad buy-in by disparate groups in the scientific community--academics, industry, and government. This is best achieved by early and frequent communication among parties and agreement on common goals. It is hoped that the creation of a validation infrastructure composed of the elements described in this report will facilitate scientific acceptance and utilization of alternative methodologies and speed implementation of replacement, reduction, and refinement alternatives in toxicity testing.

Report of the Validation and Technology Transfer Committee of the Johns Hopkins Center for Alternatives to Animal Testing. Framework for validation and implementation of in vitro toxicity tests.

The development and application of in vitro alternatives designed to reduce or replace the use of animals, or to lessen the distress and discomfort of laboratory animals, is a rapidly developing trend in toxicology. However, at present there is no formal administrative process to organize, coordinate, or evaluate validation activities. A framework capable of fostering the validation of new methods is essential for the effective transfer of new technological developments from the research laboratory into practical use. This committee has identified four essential validation resources: chemical bank(s), cell and tissue banks, a data bank, and reference laboratories. The creation of a Scientific Advisory Board composed of experts in the various aspects and endpoints of toxicity testing, and representing the academic, industrial and regulatory communities, is recommended. Test validation acceptance is contingent upon broad buy-in by disparate groups in the scientific community-academics, industry and government. This is best achieved by early and frequent communication among parties and agreement upon common goals. It is hoped that the creation of a validation infrastructure composed of the elements described in this report will facilitate scientific acceptance and utilization of alternative methodologies and speed implementation of replacement, reduction and refinement alternatives in toxicity testing.