Refinement of the Episkin protocol for the assessment of acute skin irritation of chemicals: follow-up to the ECVAM prevalidation study.

The Episkin model took part in the prevalidation study on in vitro tests for acute skin irritation of chemicals, which was carried out during 1999 and 2000. This prevalidation study was co-ordinated and supported by the European Centre for the Validation of Alternative Methods (ECVAM). During Phase 1 and Phase 2 of this study, reproducibility and transferability of the method were verified. Unfortunately, the performance of the method in terms of predictive ability was considered insufficient, due to a low specificity. In order to improve the performance of the Episkin method, the existing protocol was refined. This refinement consisted in reducing the exposure time of epidermis with chemicals. Sensitivity, specificity and accuracy of the new method were 70, 80 and 75%, respectively, thus meeting the acceptance criteria as defined by the Management Team. The Episkin method is now ready to enter a validation study of in vitro tests for acute skin irritation.

Use of human reconstituted epidermis Episkin for assessment of weak phototoxic potential of chemical compounds.

BACKGROUND/PURPOSE: Drug-induced phototoxicity is a non-immunological inflammatory skin reaction, caused by concurrent topical or systemic exposure to a specific molecule and ultraviolet radiation. Most of phototoxic compounds absorb energy particularly from UVA light leading to activated derivatives, which can induce cellular damage. This type of adverse cutaneous response can be reproduced, in vitro, using human skin models. In this study, we investigated the ability of human reconstituted epidermis Episkin to assess skin phototoxicity of weak phototoxic compounds such as 6-methylcoumarin and ofloxacin, compared to a strong one, chlorpromazine, and two negative controls (sodium dodecyl sulphate (SDS), sulisobenzone). METHODS: : After 1 h incubation with five test concentrations of each chemical compound, epidermis was then exposed or not to UVA at a non-cytotoxic dose (50 J/cm2). 18 h after UVA exposure, cellular damage was evaluated measuring cytotoxicity by MTT conversion test; in addition, pro-inflammatory mediator IL-1alpha release was also investigated. RESULTS: Topical pretreatment of Episkin, with weak phototoxic compounds induced, after UVA exposure, a dose-dependent decrease in cell viability, in concordance with an increasing IL-1alpha release. Moreover, compared to chlorpromazine, the lower IL-1alpha release observed with 6-methylcoumarin and ofloxacin could be linked to their weak phototoxic potential. CONCLUSION: Human reconstituted epidermis Episkin can be useful to study in vitro the onset of cutaneous phototoxic reactions and particularly to identify weak phototoxic compounds.

A prevalidation study on in vitro tests for acute skin irritation. results and evaluation by the Management Team.

A prevalidation study on in vitro tests for acute skin irritation was conducted during 1999 and 2000. The overall objective of validation in this area, of which this prevalidation study is an initial stage, is to identify tests capable of discriminating irritants (I) from non-irritants (NI), as defined according to European Union (EU) risk phrases ("R38"; no classification) and the harmonised OECD criteria ("Irritant"; no label). This prevalidation study specifically addressed aspects of: protocol refinement (phase I), protocol transfer (phase II), and protocol performance (phase III), in accordance with the prevalidation scheme defined by the European Centre for the Validation of Alternative Methods (ECVAM). The tests evaluated were: EpiDerm (phases I, II and III), EPISKIN (phases I, II and III), PREDISKIN (phases I and II, and additional protocol refinement), the non-perfused pig ear method (phases I and II, and additional protocol refinement), and the mouse skin integrity function test (SIFT; phases I and II). Modified, standardised test protocols and well-defined prediction models were available for each of the tests at the end of phase I. The results of phase I (intralaboratory reproducibility) were sufficiently promising for all of the tests to progress to phase II. Protocol transfer between the Lead Laboratory and Laboratory 2 was undertaken for all five tests during phase II, and additional refinements were made to the test protocols. For EpiDerm, EPISKIN and the SIFT, the intralaboratory and interlaboratory reproducibilities were acceptable; however, better standardisation of certain aspects of the test protocols was needed prior to commencing phase III. Neither PREDISKIN nor the pig ear test performed sufficiently well in phase II to progress to phase III. The PREDISKIN protocol was overly sensitive, resulting in the prediction of all the NI chemicals as I. The variability in the pig ear test results was too great, indicating that the test would show limited predictive ability. In additional studies (a repeat of phase I), further modification of the PREDISKIN protocol and a change in the prediction model considerably improved the ability of the test to distinguish I from NI chemicals. However, attempts to improve the intralaboratory reproducibility of the pig ear test were unsuccessful. In phase III an initial assessment of the reproducibility and predictive ability, in three independent laboratories per test, was undertaken for the EpiDerm and EPISKIN tests (the SIFT was a late inclusion in the prevalidation study, and is being evaluated in a separate phase III study). A set of 20 coded chemicals (10 I, 10 NI) were tested with the final, refined, test protocols. The intralaboratory reproducibility was acceptable for both EpiDerm and EPISKIN. The interlaboratory reproducibility was considered to be acceptable for EPISKIN; however, for EpiDerm, analysis of variance (ANOVA) indicated that there was a statistically significant laboratory effect on the overall variability, suggesting that the interlaboratory transferability of the test needs to be improved. The EpiDerm test had an overall accuracy of 58%, with an over-prediction rate of 37% and an under-prediction rate of 47%. The EPISKIN test had an overall accuracy of 58%, showing an under-prediction rate of 23% and an over-prediction rate of 60%. It is concluded that, as yet, none of the tests evaluated in this prevalidation study are ready for inclusion in a formal validation study on in vitro tests for acute skin irritation. Overall protocol performance of the SIFT is currently being evaluated in a phase III study. Further studies are also in progress to improve the test protocols and prediction models for EpiDerm and EPISKIN.

Cognitive socialization across ethnocultural contexts: literacy and cultural differences in intellectual performance and parent-child interaction.

A comparative study of parent-child interaction and its relation to children's intellectual achievement is presented. The question of cultural continuities in cognitive development was examined. The cross-national design also illustrates some of the problems encountered when such relationships are studied across social contexts in general. The results suggest that although interaction characteristics are related to children's intellectual achievement, that relation is moderated by context factors that may operate differently in each culture. The findings are discussed in terms of how literacy mediates parents' teaching styles in ways that remain culturally ingrained. Research issues and recommendations for future research and policy are discussed.

The effects of parents' assistance on middle school students' problem solving and achievement.

In this study the authors tested whether children's aptitudes in science were advanced in areas in which cognitive supports were generally present, particularly through interaction with more capable individuals. Mothers assisted their 7th-grade children in science activities. Differences in parent-child interaction were hypothesized to account for children's performance across 3 science tasks that differed in difficulty. A cooperative problem-solving style of interaction was identified through factor analysis. This interaction style was correlated significantly with the child's intellectual performance not only in the science tasks but also in school achievement. Development of science and other aptitudes in the context of activity variables that help bridge home and school cultures are discussed.

The therapeutic treatment provided in cases involving physical child abuse: a description of current practices.

OBJECTIVE: The purpose of this study was to explore the therapeutic treatment provided by mental health practitioners in cases involving physical child abuse to describe generally the amount and type of treatment provided to the abused child and other significant people involved in the abuse. METHOD: An instrument was designed to determine what therapeutic treatment was provided by practitioners in the previous year and sent to 689 mental health workers in the state of Kentucky: Licensed Clinical Social Workers, Clinical Members of the American Association of Marriage and Family Therapists, and Kentucky Department of Social Services Caseworkers. RESULTS: The family was seen as the primary client most frequently with the focus of therapy being to provide a safe environment for the child or to improve family relationships. Abused children were found to receive only seven of the 23 sessions generally provided in these cases to overcome the deleterious effects of the abuse. CONCLUSIONS: The findings indicate that physically abused children may need more treatment to overcome their traumatic experiences. Since the family and the perpetrator have therapeutic requirements, these services need to be additional sessions. While the safety of the child is of paramount importance, the victim needs appropriate and effective treatment to surmount the detrimental consequences of the maltreatment.

Adolescent identity exploration: a test of Erikson's theory of transitional crisis.

This research investigated Erikson's theory that adolescent identity exploration is associated with a variety of symptoms, such as fluctuations in ego strength, mood swings, rebelliousness, and heightened physical complaints. A sample of 82 high school students completed the Minnesota Multiphasic Personality Inventory (MMPI) and the Ego-Identity Interview. Identity exploration was correlated with 23 major clinical scales and the 14 Frequently Scored Scales of the MMPI. A factor analysis revealed seven scales loading on a single factor, which accounted for 39% of the variance in exploration. The items in the factor suggested a pattern consistent with Erikson's theory of adolescent crisis, and was labeled the Identity Exploration Crisis (IEC) factor. Adolescents who were actively engaged in identity exploration were more likely to produce a personality pattern characterized by self-doubt, confusion, disturbed thinking impulsivity, conflicts with parents and other authority figures, reduced ego strength, and increased physical symptoms.

Family functions and children's postdivorce adjustment.

Data on school-age children of divorced parents were examined to determine which dimensions of family dynamics were most associated with the children's socioemotional adjustment. Those factors found to be most significant were family roles, behavior control, and affective involvement, as well as children's reaction to and insight into the divorce, and conflict in the home after the divorce. Implications for parent education and early intervention are discussed.

Assessing child-rearing style in ecological settings: its relation to culture, social class, early age intervention and scholastic achievement.

Middle- and lower-class black and white adolescents were observed interacting with their mothers during a discussion of seven child-rearing problems. Maternal references to a range of disciplinary measures were identified, analyzed, and related to the subjects' scholastic performances concurrently. A factor analysis of process measures confirmed earlier findings based on self-report data concerning parental disciplinary style. Low SES mothers who participated in an early-age intervention and upper middle-class mothers tended to be less punitive than those in the low SES untreated group. Black mothers were less permissive than those in the white group. Parental disciplinary style was found to be significantly related to school performance. The results are discussed in terms of the development of methodological procedures for interaction analysis in semi-structured, ecological research, for the evaluation of process variables in early-age intervention follow-ups and theory relating disciplinary style to intellectual development.