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Philip A Botham

Publications and source records attributed to Philip A Botham.

6 recordsLinked to original sources
PubMed2004

The validation of in vitro methods for skin irritation.

Several alternative in vitro methods for identifying skin irritants have been developed in the last 10 years, the most promising of which use either reconstituted human skin models or animal (e.g. pig or mouse) skin organ cultures. In 1998, the European Centre for the Validation of Alternative Methods (ECVAM) commissioned a pre-validation study of five methods. Two reconstituted human skin methods (Epiderm and EPISKIN) and one animal skin model (the mouse skin integrity function test, SIFT) performed well in Phases I and II of the study (intralaboratory reproducibility and protocol transfer) and proceeded to Phase III which assessed reproducibility and predictive ability in three independent laboratories using a set of 20 coded test chemicals (10 irritants and 10 non irritants). Intralaboratory reproducibility was again acceptable for all three methods but inter-laboratory reproducibility was acceptable only for EPISKIN. The predictive ability of all three methods was also inadequate. Following refinements to the protocols of Epiderm and EPISKIN and changes to the statistical analysis of SIFT, the predictive ability was improved. In 2003, ECVAM concluded that they could proceed to a full validation study. This will be conducted in two phases and is scheduled for completion early in 2005.

Animals↗
PubMed2002

Acute systemic toxicity.

Use of the test that aimed to identify the single lethal dose of a substance that kills half the animals in a test group (the LD50 test) should finally be discontinued by the end of 2002, after many years of controversy and debate. In its stead are three recently developed alternative animal tests that significantly improve animal welfare: the fixed dose procedure, the acute toxic class method, and the up and down procedure. These tests have already undergone revision, both to improve their scientific performance and, importantly, to increase their regulatory acceptance. They can now be used within a strategy of acute toxicity testing for all types of test substances and for all regulatory and in-house purposes. In vitro cytotoxicity tests could be used (perhaps by mid-2002) as adjuncts to these alternative animal tests to improve dose level selection and reduce (at least modestly) the number of animals used. However, the total replacement of animal tests requires a considerable amount of further test development, followed by validation, which will require at least 10 yr.

Animal Testing Alternatives↗
PubMed2002

ECVAM's activities in validating alternative tests for skin corrosion and irritation.

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.

Animal Testing Alternatives↗
PubMed2002

ECVAM, ECETOC and the EU chemicals policy.

ECVAM's initiatives in validation have received significant support from the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC), especially through the provision of reference chemical data banks, which contain peer-reviewed, high-quality in vivo data on commercially available chemical substances. Chemicals have been selected from these ECETOC data banks for validation studies on alternative methods for skin corrosion and irritation and for eye irritation and, in addition, an ECETOC task force peer-reviewed the selection and classification, on the basis of in vivo data, of chemicals used in the validation of three alternative methods for developmental toxicity. More recently, ECVAM and ECETOC have been pursuing parallel initiatives on the proposed new EU chemicals policy, with the common goals of ensuring that industry and European Commission resources are used to investigate only those chemicals that pose a significant risk to human health and the environment, and that the Policy requires that any testing which is required follows the Three Rs principles of reduction, refinement and replacement.

Animal Testing Alternatives↗
PubMedDate not supplied

Follow-up to the ECVAM prevalidation study on in vitro tests for acute skin irritation. The European Centre for the Validation of Alternative Methods Skin Irritation Task Force report 2.

The European Centre for the Validation of Alternative Methods (ECVAM) Skin Irritation Task Force was established in 1996, to review the status of the development and validation of alternative tests for skin irritation and corrosion, and to identify appropriate non-animal tests for predicting human skin irritation that were sufficiently well-developed to be prevalidated and validated by ECVAM. The EpiDerm method, based on a reconstituted human skin model, was proposed as being sufficiently well advanced to enter a prevalidation (PV) study. Based on a review of test protocols, prediction models (PMs), and data submitted by test developers on ten specified chemicals, with 20% sodium lauryl sulphate as a reference standard, the task force recommended the inclusion of four other tests: EPISKIN and PREDISKIN, based on reconstituted human epidermis or on human skin; the non-perfused pig-ear test, based on pig skin; and the skin integrity function test (SIFT), with ex vivo mouse skin. The prevalidation study on these methods was funded by ECVAM, and took place during 1999-2000. The outcome of the PV study was that none of the methods was ready to enter a formal validation study, and that the protocols and PMs of the methods had to be improved in order to increase their predictive abilities. Improved protocols and PMs for the EpiDerm and EPISKIN methods, the pig ear test, and the SIFT were presented at an extended Task Force meeting held in May 2001. It was agreed that, in the short term, the performance of the revised and harmonised EpiDerm and EPISKIN methods, as well as the modified SIFT, should be evaluated in a further study with a new set of 20 test chemicals. In addition, it was decided that the SIFT and the pig ear test would be compared to see if common endpoints (transepidermal water loss, methyl green-pyronine stain) could be identified.

Animal Testing Alternatives↗