Occupational Hazard Evaluation - Continued Progress
in Reducing Use of Laboratory Animals in 2003
Creation of GlaxoSmithKline products from earliest research & development through to full-scale manufacture requires that employees work directly with or in proximity to chemicals. To safeguard worker health, GlaxoSmithKline health and safety programmes for chemicals have been organised to define health protective occupational exposure limits and provide information on unique chemical hazards. This dual approach supports design of equipment and facilities to contain and control chemicals in the workplace. It also provides appropriate information for first aid and other care in the event of accidental contact with chemicals.
Historically, achieving an understanding of the effects of chemicals in the workplace has involved use of laboratory animals as models for human systems. Growing scientific and public awareness around ethical use of laboratory animals has guided GlaxoSmithKline efforts to continuously reduce reliance on animal models for occupational toxicology testing wherever possible without compromising the worker safety programme.
Occupational toxicologists in the Corporate Environment, Health and Safety group focus on understanding the potential effects of GlaxoSmithKline drugs and the chemical building blocks for these drugs handled in research & development and manufacturing settings. Special emphasis is placed on understanding the results of possible chemical exposure to the skin, eyes, and respiratory tract (common routes of workplace chemical exposure) as well as other human systems. CEHS toxicologists have played an important role in developing a corporate programme to characterise the occupational health hazards of GlaxoSmithKline materials based on computer-generated prediction, cell and tissue culture and other methods not relying on animal testing.
Several key examples from 2003 illustrate the continuing commitment of GlaxoSmithKline to minimise use of laboratory animals in chemical hazard assessments for worker health and safety purposes:
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GlaxoSmithKline occupational toxicologists continued a long-standing commitment to demonstrate visible leadership in efforts to reduce live-subject testing to the minimum required by concern for safe-guarding workers' health. In 2003, these scientists submitted materials for several publications on the GlaxoSmithKline strategy for substituting cell and tissue culture methods into occupational toxicology assessments. Public presentation of these findings at international meetings devoted to chemical hazard assessment is slated for early 2004.
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GlaxoSmithKline reduced to zero the number of guinea pigs used for testing the potential of chemicals to act as skin allergens in 2003. In the past, the guinea pig has been extensively used to determine whether certain chemicals might cause allergy in humans. Recent advancements adopted by GlaxoSmithKline and encouraged by regulatory bodies in the UK have resulted in adoption of new methods that completely avoid the use of guinea pigs.
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During 2003, GlaxoSmithKline undertook a large project to fill gaps in the environment, health and safety database for existing chemicals and processes slated for transfer between manufacturing sites. A refined, tiered approach using computer structural analysis along with alternative assays was used to evaluate the potential of these chemicals to directly harm the eyes and skin. Utilising this approach, a 67% reduction was achieved in the number of rabbits used in studies supporting this project.
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Relying on a rich background of experience in development of alternative methods for characterisation of chemical hazards, GlaxoSmithKline scientists in 2003 designed and analysed a large study of a leading commercially available technology with the hope of recommending further reduction in use of laboratory animals in worker safety testing. Cultured human skin and eye tissue derived from continuously grown cell lines (provided commercially by SkinEthic, Nice, France) were evaluated for a variety of responses to chemical exposure. The outcome of this study provided promising results suggesting that these model systems will provide a viable means to reduce still further the use of animals in GlaxoSmithKline EHS testing.
These accomplishments confirm the effectiveness of the approach to GlaxoSmithKline health hazard determinations for research & development and commercial materials. In this approach, tiered evaluation of the potential effects of chemicals is initiated with searches for applicable information from literature databases. Structure-activity computer models are also used to predict possible effects. Initial research is complemented by evaluation of chemical parameters (such as acidic or basic character) that can contribute to possible adverse effects. In many cases, this first tier of assessment is sufficient to understand the hazards posed by chemicals making it possible to project likely effects from previously characterised materials to new materials and avoid use of laboratory animals altogether.
When insufficient or equivocal information is available from the initial tier of assessment a second tier of testing is initiated. This second tier of testing involves use of cell culture, tissue culture and bacterial models. GlaxoSmithKline scientists have adopted several animal-use reduction techniques recognised by health regulatory and advisory agencies (such as the UK Health and Safety Executive and US National Institutes of Health) to organise the second tier of evaluation. GlaxoSmithKline scientists actively develop, publicise and validate alternative methods used in the second tier to allow increased reliance on test methods not using laboratory animals. Again, results of Tier II testing exempts many materials from evaluation in animal models. Finally, only when chemical production levels reach certain high volume levels (thereby increasing the potential for inadvertent or accidental chemical exposure) are tests with laboratory animals considered. In many cases these tests are required by regulatory guidelines. Even in these cases, alternate means for identifying chemical hazards are sought, and testing is done with reduced animal numbers. Data on animals used for hazard determination is submitted for regulatory reporting and the numbers of animals involved in occupational toxicology testing are included in the animal research section of the Corporate Responsibility Report.
Consistent application of the tiered approach to chemical hazard assessment adopted in 2001 has resulted in significant refinement of testing undertaken for worker health and safety purposes and continues to yield many examples of diminished and more effective use of animals. |
