Biomedical subjects

P H Bay

Publications and source records attributed to P H Bay.

3 recordsLinked to original sources

PubMed1989

A risk assessment process for allergic contact sensitization.

This review describes an approach that has been used to assess the skin sensitization risk of new chemicals and product formulations prior to launching the new chemical or product on the market. The risk assessment process utilizes a comparative toxicological approach, in which data on the inherent toxicity of a material, and the exposure to it through manufacturing or consumer use or foreseeable misuse, are integrated and compared with data generated by 'benchmark' materials of similar chemistry or product application, or both. This approach has been valuable in providing an accurate assessment of the skin sensitization potential for a wide range of consumer products and pharmaceuticals, ranging from products with a very transient skin exposure (e.g. some paper products), to cosmetics, to products whose ingredients may be deposited on fabrics and thus result in chronic skin exposure. The risk assessment process described includes both guinea-pig (Buehler) and human skin sensitization test methodologies to evaluate inherent toxicity under relevant epicutaneous exposure conditions. Alternative guinea-pig test methods have been reported to be more sensitive than the Buehler method, particularly those employing intradermal injection of the test material in Freund's complete adjuvant (e.g. maximization test). However, by bypassing the skin barrier at induction, these methods can overstate the sensitization risk of epicutaneous exposure to weak sensitizers (Andersen and Hamann, 1983 and 1984; Matsushita et al., 1975a,b), and can understate the risk to very strong sensitizers possibly through tolerance induction (Buehler, 1985). In addition, materials are tested and classified at concentrations that may not be relevant to anticipated human exposure. The Buehler guinea-pig test data are important in assessing skin sensitization risk in the early phases of product development, where human exposure can be limited, controlled and monitored (e.g. manufacturing employees). The Buehler test can often define consumer skin sensitization risk; however, the ultimate consumer skin safety assessment should in general be developed through a series of controlled human tests; the human repeat insult patch test and, when necessary, the provocative or extended product use tests. Post-market monitoring of skin-related consumer comments is the final phase of the data gathering process. These results can be used to assess further each product and to provide valuable feedback to confirm the validity of the overall risk assessment process. Risk assessment for skin sensitization potential is seldom a simple process.(ABSTRACT TRUNCATED AT 400 WORDS)

Consumer Product Safety↗

PubMed1982

In vitro and in vivo inhibition of primary transcription of vesicular stomatitis virus by a defective interfering particle.

A unique defective interfering (DI) particle, generated by a heat-resistant (HR) mutant of Indiana serotype vesicular stomatitis virus, was capable of inhibiting primary transcription by heterologous New Jersey serotype virions. The correlation between this phenomenon and the lowering of viral yields from doubly infected cells was investigated by the construction of chimeric DI particles containing the HR DI particle genome with a thermolabile polymerase. At the nonpermissive temperature, these DI particles were unable to self-transcribe, inhibit virion primary transcription, or reduce virion yield, but were able to be replicated. These results suggested that self-transcription of the HR DI particle genome was a prerequisite for heterotypic interference, but not for its own replication. Inhibition of virion primary transcription by HR DI ribonucleocapsids was also observed in vitro. At low HR DI to virion ribonucleocapsid ratios, the extent of inhibition was concentration dependent, whereas at high ratios, the amount of inhibition was concentration independent, approaching a limiting maximum value. A speculative mathematical model, which quantitatively accounts for these data, is presented. According to this model, the higher affinity for polymerase molecules by the HR DI ribonucleocapsids is explained in terms of dissociation events during transcription, which are more frequent in the longer virion ribonucleocapsids.

Animals↗

PubMed1979

UV inactivation of the biological activity of defective interfering particles generated by vesicular stomatitis virus.

UV inactivation of vesicular stomatitis virus and its defective interfering (DI) particles was measured in order to obtain the target size for interference. In the case of DI particles whose genomes mapped at the 5' end of the virion RNA, this target size corresponded to the entire DI particle RNA molecule regardless of whether it amounted to 10, 30, or 50% of the viral genome. These data were interpreted as demonstrating that both termini of the DI particle RNAs were required for their replication and for interference with virion RNA replication. The unique heat-resistant DI particle, with an RNA molecule corresponding to the 3' half of the viral genome, exhibited an inactivation target size of approximately 42% of its RNA molecule with respect to both homotypic and heterotypic interference. Unlike other DI particles, this particle interfered with virion primary transcription. The unusual inactivation target size of the heat-resistant DI particle was interpreted as being a compromise between the requirements for replication of its genome and those for interference with virion primary transcription.

Defective Viruses↗