Harmful if swallowed

Despite a commitment to reduce animal tests by 50% by the year 2000, the EU is poised to implement a newly developed Chemicals Policy. It is estimated by the BUAV(British Union for the Abolition of Vivisection) and PETA (People for the Ethical Treatment of Animals) that the lives of as many as 10,000,000 animals would be at stake over 20 years of testing - and could potentially allow dangerous chemicals to be released into the environment. Allison Kane looks at the issues involved and argues that there are better alternatives.

The proposal to test existing and commonly used chemicals on animals would represent the largest toxicity testing in Europe’s history. For the proposed EU chemical –testing programme to have any scientific credibility at all, the test methodologies must be able to guarantee scientifically valid, and biologically relevant and reproducible tests. There is a considerable body of scientific evidence documenting the failure of animal-based toxicity studies to accurately predict human reactions to chemicals. Such errors are not surprising, given the many differences that exist between species in terms of their anatomy, physiology, biochemistry and metabolism. Nobel Laureate in Medicine, Dr. Lederberg, cautions that such variables make the cross-species extrapolation of test results an extremely uncertain exercise.

Animals are exposed to test chemicals through the following routes:

• Oral: Chemicals are generally pumped directly into the animals’ stomach via a force-feeding tube or syringe, however, the chemicals can also be ingested when added to the animals’ food. Acute oral toxicity tests cause extreme pain and distress to then animals involved.
• Inhalation: Animals are forced to breathe in chemical vapours over a fixed period of time. Often the animals are restrained and have breathing apparatuses fixed over their mouth. Effects such as nasal bleeding, laboured breathing, convulsions, coma and ultimately death are all common.
• Skin: In dermal toxicity studies, groups of rabbits, guinea pigs, or rats have their back shaved and a test substance applied in order to measure the penetration rate of a chemical through the skin.
• Repeated-dose Toxicity: The test protocol recommends exposures of lower doses via each of the oral, dermal and inhalation routes over a period of 14-90 days.
• Toxicity to Reproduction: This is designed to measure the effects of chemicals on fertility and reproductive organs. Test protocol calls for either a 28 - or a 90-day repeated-dose study. At the conclusion of the study the animal’s genitals and reproductive organs are often removed for further study.
• Developmental Toxicity: Testing is conducted to assess the potential of a chemical substance to affect developing offspring during critical periods of growth and development. These tests are carried out on pregnant rodents and commons effects from this type of poisoning can include developmental abnormalities and physical deformities, maternal toxicity, miscarriage and early embryonic death.

There are alternatives to the above. At present, a tiered approach combining computer modelling of quantitative structure-activity relationships (QSAR’S) and a battery of four or more in vitro cell toxicity tests is believed to be the most promising replacement to animal use in acute toxicity testing. Such an approach has already been found to predict human toxicity with an impressive 84% accuracy rate. The absorption of chemical through the skin can now be conducted using skin from cadavers and established in vitro diffusion techniques. Alternative methods proposed as replacements for repeated-dose toxicity include in vitro cultures of various organ tissues. Human cell cultures have been established for kidney, nervous, immune, reproductive and other essential organ systems. More generally computer-based modelling approaches have shown great promise in providing an alternative. Structure-Activity Relationships (SAR’S) use computers to seek to predict adverse biological effects of chemicals based on their molecular structure, weight and electronic charge. SAR data can be used to estimate whether a specific chemical produces a particular biological response, including toxicity, without recourse to animals. It is now possible to use computers to model living biological systems, such as the human circulatory and respiratory systems. For example, physiological based bio-kinetic models (PBBK’S) use computers to study the absorption, distribution, metabolism and excretion of a chemical by the body. One such model, the EDO1, studies tumour production in response to chemical exposure. It can detect an increased tumour activity of 1%, and at doses of a chemical much lower than those customarily used in rodent studies.

There are barriers both legislative and regulatory to reliance on the methodologies briefly outlined above. However, the revision of the EU chemical policy provides us with a unique opportunity to force the European Commission to reassess its current approach to chemical testing and regulation. The Commission is now in a position to initiate a new testing programme using efficient and humane methods. The following approach urgently needs to be implemented.

• Mandatory data sharing between companies and countries to make use of the maximum amount of existing chemicals data and avoid duplicative testing would also save the torment and death of countless animals.
• Postponements of the proposed testing programme for a minimum of 3 years in order to prioritise the validation of promising new in vitro methods.
• Harmonise the international validation process.
• Screen priority chemicals through rapid, non-animal tests (such as “stepwise strategies” already accepted by the OECD.

Such a targeted approach by EU to modernise its chemical-testing strategy would demonstrate a clear commitment to developing the most reliable and accurate test methods. This approach would also be in accordance with EU Directive 86/609, which forbids the use of animals in experiments where an alternative method is reasonably and practically available.