LABORATRY TESTING FOR REACH
This short guide has been provided to give a brief overview of the typical ‘base-set’ of testing needed to provide classification and labelling endpoints and to enable a reasonable risk assessment to be constructed.
A more detailed guide can be provided on request info@denehurst.co.uk
Before considering the individual test methods, it is necessary to look at the studies in context of the ‘intelligent testing strategy’ that describes the order in which the testing should be performed. Although each test is described separately, the results of one study can have a major impact on planning the next test – this is an essential part of constructing the intelligent testing strategy and such strategy is described in guidance provided by ECHA. This basically means that you should resist the temptation to place all studies in one go without waiting for the result of initial work.
In this guide, the methods are listed in order of the IUCLID data entry ‘end-points’
Guidelines and GLP
Full regulatory testing for environmental and health effects should be performed compliance with international Good Laboratory Practice (GLP). However, older test reports for animal studies that were not performed to GLP can be accepted under certain circumstances if it can be demonstrated that repeating animal work is to be avoided.
Chemical identity and physico-chemical properties do not need to be performed to GLP.
Intelligent test strategy
A large amount of guidance has been provided to cover what is known as the ‘intelligent test strategy’ to ensure that animal testing is minimised through stressing the importance of using existing data, modelling and read-across techniques.
Note that all end-points in each respective tonnage band must be assessed either by testing, consideration of non-test data (modelling etc) or by exposure consideration. Certain studies may be impossible or irrelevant according to the nature of the substance; for example, biodegradation cannot be performed on inorganic substances.
Article 26 Inquiry
Remember that the first step is always the Article 26 Inquiry to confirm substance identity and if you are not aware of other Registration holders, you will need to indicate which new testing you plan. An outcome of the Inquiry is that ECHA (EU REACH) or HSE (GB REACH) will inform you if other data exists and how you can gain access. Lists of other relevant Registration holders will be provided and you will be expected to share at last the animal tests.
* Impacts on CLP / GHS classification
| IUCLID endpoint | KEY STUDIES | Comments |
| Recommended for all registrants | The first set of studies are typically necessary for transport classification as a minimum | |
| Section 1 | Product characterisation, spectra, analysis etc | Essential and needed for Article 26 Inquiry. Required for all registrants, including those involved in joint registrations |
| Initial assessment to plan testing | Also needed for SDS and Transport classification | |
| 4.1 4.2 4.3 4.4 4.5 4.8 4.11 4.13 4.14 4.12 4.15 | Physical state Melting point/setting point Boiling point Relative density Particle size (granulometry) Water solubility – assess Flash point* Flammability* Explosivity* Autoflammability (self-ignition)* Oxidising properties (solids)* | Essential DSC analysis usually sufficient. DSC analysis. Solids only – indicates need for inhalation toxicity Stability in water? Measured pH? Essential for liquids below 60°C Essential for solid below 60°C Structure analysis as a minimum Test if chemical structure or DSC indicates concern Structure analysis as a minimum |
| Required for 1 – 10 tonnes | The results of the first set are necessary to plan these studies in phase 2 Phase 2 end-points are needed to allow full use of models and to allow a reasonable level of confidence for read-across as well as enabling planning for further tests. | |
| 4.6 4.7 4.8 4.10 5.2.1 6.1.5 6.1.3 7.2 7.3.1 7.3.2 7.4.1 7.6.1 | Vapour pressure Partition coefficient* Water solubility Surface tension in water Ready biodegradation* Daphnia immobilisation* Inhibition to algae Acute toxicity (oral ?)* Skin irritation* Eye irritation* Skin sensitisation* Bacterial gene mutation (Ames test) | May not be required if melting point is over 200°C. Modelling may help. Results will help predict inhalation risk or environmental fate. Key study for environmental fate. Normal to assess to 1 mg/l minimum by analysis. Will impact on further testing. Check stability. Water solubility, stability and vapour pressure will help determine the method. Easiest (cheapest) of the short-term environmental effects. Supporting analysis needed Unless a gas, or under other exceptional circumstances, oral administration is the first method In-vitro. In-vitro. In-vitro methods The first level of mutagenicity assessment – a positive result will lead to further immediate testing |
| Required for 10 – 100 T | These tests should only be performed after considering results of phase 1 and 2 evaluation. | |
| 5.1.2 5.4.1 6.1.1 6.1.7 7.2 7.5/7.8 7.6.1 | Abiotic degradation (hydrolysis) Adsorption screening Short term fish toxicity * Bacterial inhibition Acute toxicity (inhalation or dermal)* Sub-acute toxicity (28 day)* with reproduction screen In vitro cytotoxicity In vitro gene mutation, mammal cells | Only possible to perform if water solubility is > 10 mg/l. Attempt to identify the degradation products. Basic HPLC method based on results of partition coefficient and structure analysis. Indication of stability should be assessed early in the programme, and analysis from Daphnia or algal studies will indicate problems. Depends on product properties and exposure Typically oral, gavage, but other routes and methods may be considered in view of potential exposure risk For example, chromosome aberration, but choice of method determined by results of bacterial gene mutation (Ames) |
| 7.1 | Toxicokinetic assessment | Use all available information derived by this stage to construct scientific assessment of behaviour in biological systems. Essential conclusion to the robust summary. Up-date if further testing performed after this stage |
| > 100 tonnes or as a result of adverse findings in earlier phases | These studies must not be performed without due consideration of exposure risk as a result of conclusions determined from the Chemical Safety Assessment. Proposals for animal tests must be submitted to ECHA | |
| 4.1.7 4.21 7.1 7.5 7.6.2 7.8.2 7.8.1 7.7 | Solvent stability Dissociation constant Toxicokinetic testing – ADME In-vivo mutagenicity* Sub-chronic mammalian toxicity* Teratogenicity (rat or rabbit)* One or two generation toxicity studies* Carcinogenicity studies* | Consider if breakdown in polar or non-polar solvents is likely from structure analysis Consider if reasonably soluble in water and if structure analysis suggests dissociation. Check pH. Metabolism studies (Absorption, Distribution, Metabolism and Excretion) should be performed to assess possible elimination and accumulation effects in mammals. This may preclude chronic testing if removal is evident. As well as further in-vitro studies, in-vivo methods can be considered if results of earlier testing show positive or equivocal results or if very high exposure predicted to the consumer. Typically 90 days. Route or administration determined by risk factors, but usually oral. Pre-natal development. Reproduction studies are expected and ‘extended one-generation method considered suitable. A full 2-year chronic / carcinogenicity needs to be considered if high exposure and if results of other studies, for example mutagenicity, suggest a cause for concern. |
| EXPOSURE –BASED STUDIES | Consider only if there is risk of exposure to the aquatic or terrestrial environment due to high levels of use, exposure scenarios, or as a result of biodegradation, solubility, stability or partitioning results | |
| 6.1 5.2.2 5.3 6.3 | ENVIRONMENTAL EFFECTS STUDIES* Inherent and soil biodegradation* Bioconcentration* Terrestrial testing | A range of long-term and reproduction studies can be performed on fish or other aquatic organisms to examine chronic or life-cycle effects. Consider if high exposure to aquatic or marine environments or if poorly degradable in water. Various methods possible to determine if there is a problem with persistence. Consider if there substance is a candidate for vPvB or PBT. Consider if partition coefficient is > log 4 and if poor biodegradability. Not relevant if molecular weight above 1000. Soil organisms, plants and even birds can be tested, but only consider if there is a high risk of exposure to the soil and the substance is poorly degradable. |