There are many different chemicals and materials in use today. These are subject to stringent regulations, which include a requirement for physico-chemical and toxicity testing. In some countries existing chemicals are also undergoing safety checks. The aim is to determine their hazardous properties and the risks involved in using substances.

Health and safety of the environment and the individual are becoming of prime importance to society and extensive legislation has been developed. To the R&D chemist this is a maze to negotiate when trying to introduce a new material or chemical into a different market place. What tests are required and for which markets What do the test results mean Who are the key organisations in each global region Legislation varies between applications and often the quantity of chemical in use is critical to determining the level of testing required.

A Practical Guide to Chemical Safety Testing describes the different tests that must be performed on new chemicals and other materials to demonstrate to the regulatory authorities that they are safe for use. Tests vary from physico-chemical, measuring properties such as melting point and density, through genetic toxicity studies, to mammalian toxicology and studies to investigate effects on the environment. Animal testing is carried out to look for potential irritants, harmful substances, corrosive agents, allergens, cancer causing potential, etc. Each test type is described here and the validity of the test methods is debated. For example, there are sometimes major differences between simple model systems using cell lines or bacteria, effects in laboratory animals and, most importantly, with effects on humans. This can give rise to misleading interpretation of results.

There is a chapter devoted to alternatives to animal testing for safety evaluation. Many non-animal screening tests are available. It is also becoming increasingly possible to cross-match many new chemicals with existing toxicity data to predict potential carcinogenicity, allergenicity, etc. These approaches can reduce the test requirements for the chemical, although a structural alert showing the presence of a suspect chemical moiety can trigger definitive toxicological assessment.

Ecotoxicological testing is carried out to determine the level of hazard to organisms in the environment. Important properties used to estimate environmental fate include the solubility of the test material in water, its ability to adsorb to soil and its potential for accumulation in animals.

Regulations vary depending on the intended purpose of a material, and this book describes the requirements for general chemicals, polymers, food contact materials, medical devices and biocides. Often the quantity imported into a region determines the stringency of the testing required. The EU, the USA, Japan and other geographical regions each has its own set of regulations. These are outlined here. In some instances approval of a chemical in one country will lead to automatic approval in a second country. In other cases new testing is required. This is a very complex situation. The second half of this book sets out to untangle the web of legal issues facing manufacturers and suppliers.

This book is essential reading for chemical and material manufacturers and suppliers. It describes clearly the process of obtaining approval for use in a variety of global regions and across different applications. It also explains why different tests are performed and the implications of the results.

Key features

• Physico-chemical testing
• Genetic toxicity testing
• Ecotoxicity testing
• Animal testing
• Regulations
• Risk assessment
• Chemicals
• Food packaging
• Medical devices
• Polymers

  About the author
  Dr Derek Knight is the Director of Regulatory Affairs at Safepharm Laboratories Ltd. He is an expert in regulatory requirements, providing advice on testing and document submission to regulatory authorities. He has a
  
  
  1 Introduction
  1.1 Purpose of the Book
  1.2 Purpose of Safety Evaluation
  1.3 Safety Studies
  1.4 Risk Assessment and Safety Data
  1.5 Regulatory Schemes
  1.6 Summary

  2 Mammalian Toxicology
  2.1 Introduction
  2.2 Acute Toxicity Studies
  2.2.1 Nature and Relevance of Tests
  2.2.2 Methodology
  2.2.3 Acute Oral Toxicity Studies
  2.2.4 Dermal Toxicity Studies
  2.2.5 Inhalation Toxicity Studies
  2.2.6 Alternative Acute Oral Toxicity Methods
  2.2.7 Local Tolerance Tests
  2.2.8 Contact Sensitisation
  2.3 Repeated Dose Toxicity Studies
  2.3.1 Nature and Relevance of Tests
  2.3.2 Importance of Repeated Dose Toxicity
  2.3.3 Methodology
  2.4 Reproduction Toxicology
  2.4.1 Nature and Relevance of Tests
  2.4.2 Methodology
  2.4.3 Alternative Approaches
  2.5 Carcinogenicity
  2.5.1 Nature and Relevance of Tests
  2.5.2 Methodology
  2.5.3 Dose Levels
  2.5.4 Conduct of Study
  2.5.5 Data Evaluation
  2.5.6 Risk Assessment
  2.5.7 Alternative Approaches
  2.6 Medical Device Testing
  2.6.1 Exposure Routes
  2.6.2 Dose Preparation
  2.6.3 Cytotoxicity Testing of Medical Devices

  3 Genetic Toxicology
  3.1 Introduction
  3.2 Mechanisms of Mutation - Genes and Chromosomes
  3.3 Standard Genetic Toxicology Assays
  3.4 Bacterial Mutagenicity Assays
  3.5 Chromosome Aberration Tests In Vitro
  3.6 Mammalian Cell Gene Mutation Assays In Vitro
  3.7 The In Vivo Micronucleus Test
  3.8 The Unscheduled DNA Synthesis Assay
  3.9 Conclusions

  4 Ecotoxicology
  4.1 Introduction
  4.2 Bacterial Toxicity Testing
  4.3 Biodegradation Tests
  4.3.1 Ready Biodegradation Tests
  4.3.2 Inherent Biodegradation Tests
  4.3.3 Simulation Tests
  4.3.4 Anaerobic Biodegradation Tests
  4.4 Aquatic Toxicity Testing
  4.4.1 Acute Tests
  4.4.2 Analytical Measurements
  4.4.3 Difficult Substances
  4.4.4 Chronic Tests
  4.5 Fish Bioaccumulation Test
  4.6 Sediment Toxicity Tests
  4.7 Terrestrial Toxicity Tests
  4.7.1 Earthworms
  4.7.2 Bees and Beneficials
  4.7.3 Plant Growth Tests
  4.8 Microcosm and Mesocosm Studies
  4.9 Conclusion

  5 Physico-Chemical Properties
  5.1 Introduction
  5.2 Performance of the General Physico-Chemical Tests
  5.2.1 Melting Temperature/Melting Range (OECD Test Guideline 102)
  5.2.2 Boiling Point (OECD Test Guideline 103)
  5.2.3 Vapour Pressure (OECD Test Guideline 104)
  5.2.4 Water Solubility (OECD Test Guideline 105)
  5.2.5 Partition Coefficient (OECD Test Guidelines and 117)
  5.2.6 Adsorption Coefficient (OECD Test Guidelines 106 and 121)
  5.2.7 Density/Relative Density (OECD Test Guideline 109)
  5.2.8 Particle Size Distribution (OECD Test Guideline 110)
  5.2.9 Hydrolysis as a Function of pH (OECD Test Guideline 111)
  5.2.10 Dissociation Constant (OECD Test Guideline 112)
  5.2.11 Surface Tension (OECD Test Guideline 115)
  5.2.12 Fat Solubility (OECD Test Guideline 116)
  5.3 Performance of the Polymer Specific Physico-Chemical Tests
  5.3.1 Number-Average Molecular Weight and Molecular Weight Distribution of Polymers (OECD Test Guideline 118)
  5.3.2 Solution/Extraction Behaviour of Polymers in Water (OECD Test Guideline 120)
  5.4 Performance of the Hazardous Physico-Chemical Tests
  5.4.1 Flash Point (EC Method A9)
  5.4.2 Flammable Solids (EC Method A10)
  5.4.3 Flammable Gases (EC Method A11), Flammable Substances on Contact with Water (EC Method A12) and Substances Liable to Spontaneous Combustion (EC Method A13)
  5.4.4 Explosive Properties (EC Method A14)
  5.4.5 Auto-ignition Temperature, Liquids and Gases (EC Method A15) and Relative Self-ignition Temperature, Solids (EC Method A16)
  5.4.6 Oxidising Properties (EC Method A17)
  5.5 Order in which Physico-Chemical Tests are Performed
  5.6 Conclusion

  6 Alternatives to Animal Testing for Sa