Follow-up to the ECVAM Prevalidation Study on In Vitro Tests for Acute Skin Irritation

2002 ◽  
Vol 30 (1) ◽  
pp. 109-129 ◽  
Author(s):  
Valérie Zuang ◽  
Michael Balls ◽  
Philip A. Botham ◽  
Alain Coquette ◽  
Emanuela Corsini ◽  
...  
Keyword(s):  
Skin Irritation ◽  
In Vitro Tests

scholarly journals Formulations Based on Drug Loaded Aptamer-Conjugated Liposomes as a Viable Strategy for the Topical Treatment of Basal Cell Carcinoma—In Vitro Tests

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 866
Author(s):  
Anca N. Cadinoiu ◽  
Delia M. Rata ◽  
Leonard I. Atanase ◽  
Cosmin T. Mihai ◽  
Simona E. Bacaita ◽  
...  
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Topical Treatment ◽  
Skin Irritation ◽  
In Vitro Tests ◽  
Liposomal Drug ◽  
Liposomal Formulations ◽  
As1411 Aptamer

Topical liposomal drug formulations containing AS1411-aptamer conjugated liposomes were designed to deliver in a sustained way the 5-fluorouracil to the tumor site but also to increase the compliance of patients with basal cell carcinoma. The 5-fluorouracil penetrability efficiency through the Strat-M membrane and the skin irritation potential of the obtained topical liposomal formulations were evaluated in vitro and the Korsmeyer Peppas equation was considered as the most appropriate to model the drug release. Additionally, the efficiency of cytostatic activity for targeted antitumor therapy and the hemolytic capacity were performed in vitro. The obtained results showed that the optimal liposomal formulation is a crosslinked gel based on sodium alginate and hyaluronic acid containing AS1411-aptamer conjugated liposomes loaded with 5-fluorouracil, which appeared to have favorable biosafety effects and may be used as a new therapeutic approach for the topical treatment of basal cell carcinoma.

A prevalidation study on in vitro tests for acute skin irritation

2001 ◽  
Vol 15 (1) ◽  
pp. 57-93 ◽  
Author(s):  
J.H Fentem ◽  
D Briggs ◽  
C Chesné ◽  
G.R Elliott ◽  
J.W Harbell ◽  
...  
Keyword(s):  
Skin Irritation ◽  
In Vitro Tests

Alternative Methods for Skin Irritation Testing: The Current Status

1998 ◽  
Vol 26 (2) ◽  
pp. 195-211 ◽  
Author(s):  
Philip A. Botham ◽  
Lesley K. Earl ◽  
Julia H. Fentem ◽  
Roland Roguet ◽  
Johannes J.M. van de Sandt
Keyword(s):  
Prediction Model ◽  
Human Skin ◽  
Task Force ◽  
Skin Irritation ◽  
Alternative Methods ◽  
Current Status ◽  
In Vitro Tests ◽  
Structure Property ◽  
Test Protocol

The ECVAM Skin Irritation Task Force was established in November 1996, primarily to prepare a report on the current status of the development and validation of alternative tests for skin irritation and corrosion and, in particular, to identify any appropriate non-animal tests for predicting human skin irritation which were sufficiently well-developed to warrant ECVAM supporting their prevalidation/validation. The task force based its discussions around the proposed testing strategy for skin irritation/corrosion emanating from an OECD workshop held in January 1996. The following have been reviewed: a) structure-activity and structure-property relationships for skin corrosion and irritation; b) the use of pH and acid/alkaline reserve measurements in predicting skin corrosivity; c) in vitro tests for skin corrosion; d) in vitro tests for skin irritation (keratinocyte cultures, organ cultures, and reconstituted human skin models); and e) human patch tests for skin irritation. It was apparent that, although several promising candidate in vitro tests for skin irritation (for example, reconstituted human skin methods, and human and animal skin organ culture methods) were under development and evaluation, a test protocol, a preliminary prediction model and supporting data on different types of chemicals were only available for a method employing EpiDerm™. Thus, it is proposed that this EpiDerm test undergoes prevalidation during 1998. In addition, since it was felt preferable to be able to include other in vitro tests in such a prevalidation study, it is recommended that a “challenge” be set to anyone interested in taking part. This involves submitting data on ten test chemicals selected by the task force, obtained according to a standard protocol with a preliminary prediction model, for review by the task force by 31 May 1998.

The In Vitro Acute Skin Irritation of Chemicals: Optimisation of the EPISKIN Prediction Model within the Framework of the ECVAM Validation Process

2005 ◽  
Vol 33 (4) ◽  
pp. 329-349 ◽  
Author(s):  
José Cotovio ◽  
Marie-Hélène Grandidier ◽  
Pascal Portes ◽  
Roland Roguet ◽  
Gilles Rubinstenn
Keyword(s):  
Prediction Model ◽  
Mtt Assay ◽  
Skin Irritation ◽  
Membrane Damage ◽  
Clinical Signs ◽  
Alternative Methods ◽  
In Vitro Tests ◽  
Validation Process

In view of the increasing need to identify non-animal tests able to predict acute skin irritation of chemicals, the European Centre for the Validation of Alternative Methods (ECVAM) focused on the evaluation of appropriate in vitro models. In vitro tests should be capable of discriminating between irritant (I) chemicals (EU risk: R38) and non-irritant (NI) chemicals (EU risk: “no classification”). Since major in vivo skin irritation assays rely on visual scoring, it is still a challenge to correlate in vivo clinical signs with in vitro biochemical measurements. Being particularly suited to test raw materials or chemicals with a wide variety of physical properties, in vitro skin models resembling in vivo human skin were involved in prevalidation processes. Among many other factors, cytotoxicity is known to trigger irritation processes, and can therefore be a first common event for irritants. A refined protocol (protocol15min–18hours) for the EPISKIN model had been proposed for inclusion in the ECVAM formal validation study. A further improvement on this protocol, mainly based on a post-treatment incubation period of 42 hours (protocol15min–42hours), the optimised protocol, was applied to a set of 48 chemicals. The sensitivity, specificity and accuracy with the MTT assay-based prediction model (PM) were 85%, 78.6% and 81.3% respectively, with a low rate of false negatives (12%). The improved performance of this optimised protocol was confirmed by a higher robustness (homogeneity of individual responses) and a better discrimination between the I and NI classes. To improve the MTT viability-based PM, the release of a membrane damage marker, adenylate kinase (AK), and of cytokines IL-1α and IL-8 were also investigated. Combining these endpoints, a simple two-tiered strategy (TTS) was developed, with the MTT assay as the first, sort-out, stage. This resulted in a clear increase in sensitivity to 95%, and a fall in the false-positive rate (to 4.3%), thus demonstrating its usefulness as a “decision-making” tool. The optimised protocol proved, both by its higher performances and by its robustness, to be a good candidate for the validation process, as well as a potential alternative method for assessing acute skin irritation.

The ECVAM International Validation Study on In Vitro Tests for Acute Skin Irritation: Selection of Test Chemicals

2007 ◽  
Vol 35 (6) ◽  
pp. 603-619 ◽  
Author(s):  
Chantra Eskes ◽  
Thomas Cole ◽  
Sebastian Hoffmann ◽  
Andrew Worth ◽  
Amanda Cockshott ◽  
...  
Keyword(s):  
Validation Study ◽  
Skin Irritation ◽  
In Vitro Tests ◽  
Selection Of

Pertechnetate Uptake in the Prediction of Early Outcome after Radioiodine Therapy

1989 ◽  
Vol 28 (01) ◽  
pp. 21-25
Author(s):  
T. M. D. Gimlette
Keyword(s):  
Positive Predictive Value ◽  
Radioiodine Therapy ◽  
In Vitro Tests ◽  
First Year ◽  
Thyroid Antibodies ◽  
Early Outcome ◽  
Before And After ◽  
Uptake Test

99mTc-pertechnetate uptake was estimated 8-13 weeks after radioiodine therapy for hyperthyroidism in 132 patients in order to evaluate the usefulness of the uptake test in predicting both persisting hyperthyroidism and the early onset of hypothyroidism during the first year after therapy. The estimation was simple, the result immediately available, and its sensitivities, positive predictive value and its overall accuracy (83%) compared favourably with that of in-vitro tests, FT4I (75%) and FT3I (80%), carried out on the same occasions during the early follow-up period. Pertechnetate uptake can be a useful guide to management by promptly identifying patients likely to need further radioiodine therapy and those with transient or permanent hypothyroidism. The study confirmed some previous findings that hypothyroidism was more frequent in patients with thyroid antibodies and less frequent in patients with nodular thyroids, and it also indicated that hypothyroidism was more frequent in those treated with carbimazole before and after radioiodine, and that hyperthyroidism was more likely to persist in those treated with carbimazole before or after radioiodine.

ECVAM's Activities in Validating Alternative Tests for Skin Corrosion and Irritation

2002 ◽  
Vol 30 (2_suppl) ◽  
pp. 61-67 ◽  
Author(s):  
Julia H. Fentem ◽  
Philip A. Botham
Keyword(s):  
Human Skin ◽  
Validation Study ◽  
Task Force ◽  
Skin Irritation ◽  
Test Method ◽  
Performance Criteria ◽  
In Vitro Tests ◽  
Rat Skin ◽  
Formal Validation

ECVAM has funded and managed validation studies on in vitro tests for skin corrosion, resulting in the validities of four in vitro tests being endorsed by the ECVAM Scientific Advisory Committee: the rat skin transcutaneous electrical resistance (TER) assay, two tests based on the use of commercial reconstituted human skin equivalents, EPISKIN™ and EpiDerm™, and another commercially-produced test, CORROSITEX®. In the European Union (EU), a new test method on skin corrosion (B.40), incorporating the rat skin TER and human skin model assays, was included in Annex V of Directive 67/548/EEC in mid-2000, thereby making the use of in vitro alternatives for skin corrosion testing of chemicals mandatory in the EU. At the recommendation of its Skin Irritation Task Force, ECVAM has funded prevalidation studies on five in vitro tests for acute skin irritation: EpiDerm, EPISKIN, PREDISKIN™, the pig-ear test, and the mouse-skin integrity function test (SIFT). However, none of the tests met the criteria (set by the Management Team for the studies) for inclusion in a large-scale formal validation study. Thus, to date, there are no validated in vitro tests for predicting the dermal irritancy of chemicals. Following further work on the EPISKIN, EpiDerm and SIFT test protocols and/or prediction models after the completion of the prevalidation studies, it appears that the modified tests could meet the performance criteria defined for progression to a validation study. This will now be assessed independently by the ECVAM Skin Irritation Task Force, with the objective of taking a decision before the end of 2002 on whether to conduct a formal validation study.

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