Registration data requirements

To register substances under REACH, there are defined data endpoints that need to be assessed dependant on tonnage.  The lists are reproduced in the Appendix  below, together with comments on waiver opportunities.

 

ECHA guidance for data assessment is split into a number of chapters and the first chapters relate to assessment of existing data, use of models etc and this makes it very clear that laboratory testing is a last resort when existing data or other methods of assessment are not justified.  There is also an important objective to avoid animal testing where-ever possible.

 

The waiver relevant for synthesis or industrial use of substances failing the SCC intermediate criteria will be the ‘exposure considerations’.  These are defined in detail below and specific end-points described in the Appendix.

 

Note that waivers based on exposure do not generally apply to any substance used in non-industrial settings and only apply if the Exposure Scenarios and SDSs are explicit in the need for extensive and effective control.

 

Acute toxicity, skin and eye irritation

The toxicological concern is based on single accidental exposure of relatively large quantities resulting from spillages, maintenance work and exposure during handling.  If the processes are fully contained and it can be demonstrated that during manufacture and use there is sufficient control and awareness in place to prevent any exposure, exposure waivers could be justified. 

 

However, for transported intermediates and substances, there is an expectation of some assessment for accidental exposure and subsequent classification for transport and supply.  As a minimum, in-vitro skin and eye irritation should be assessed.  Note that there is no justification for in-vivo rabbit studies and waivers for animal studies are more likely to be upheld than no-animal assessments. 

 

Sensitisation, repeat toxicity, mutagenicity, reproduction etc.

The justification that there is no exposure to small concentrations over longer periods of time is difficult to justify.  Note that workplace monitoring demands can be added to Exposure Scenarios and SDS – ie. users not monitoring the workplace are not within the conditions stipulated in the registration. Data from workplace monitoring can be added to the CSR to add weight to the effectiveness of the conditions for control.

 

For these endpoints, read-across and modelling will need to be added to the waivers to add weight to the justification to avoid new studies.  The justification to avoid in-vitro mutagenicity endpoints is weakened as these can be done without involving animals. 

 

Sludge inhibition, biodegradation, partition-coefficient, etc

If all waste is collected at sites of manufacture and use (including exhaust extractions), then it can be argued that there is no environmental exposure.  However, the odd spill and contamination from cleaning safety equipment or from quality control laboratories make 100% control difficult to achieve. 

 

Effects on sewage treatment and basic degradation data do need to be assessed if there are even trace quantities lost to the environment and failure to perform base-level studies is hard to justify – especially as no animals are harmed in doing so.

 

Aquatic studies- short term

If there is no known loss to the environment and assessments show degradation (see above), then exposure waivers could be argued.  However, simple non-vertebrate studies such as Daphnia inhibition are difficult to justify not performing.  If no effect, or if effects match models or read-across estimates, further testing should be possible to avoid and models may be possible to justify for fish and algae.

Aquatic studies – long term (chronic)

If degrading in the environment and minimal risk of exposure, waivers and assessments are generally possible to justify.

 

Terrestrial and sediment studies

Only if there is loss to municipal waste treatment works where sludge is used as fertiliser and where there is no biodegradation and tendency to adsorb to solids, do these studies need performing.  For use at industrial sites where on-site treatment ensures solids are disposed of as chemical waste, waivers are possible to justify with little debate.

 

 

The importance of the CSR and the Exposure Scenarios backing up the waiver justifications cannot be stressed enough.  The ES must provide explicit instructions on how to control risk and must point out that failure to meet the levels of control will lead to unacceptable levels of exposure.  If users cannot meet the strict conditions, further data endpoints will need to be assessed in detail, with more laboratory work if needed.

 

Conclusions

The term ‘strictly controlled conditions’ describes the ultimate level of control, and will lead to reduced mandated data assessment for classes of substance that are considered intermediates.

 

However, exposure based waivers are possible to justify for industrial scenarios of use where there are highly controlled conditions and where the substances are consumed and do not get passed on to non-industrial users. 

 

The justification to use models, read-across or waivers for registration to reduce laboratory testing costs will be easier to demonstrate where there is low exposure and good controls in place. 

 

Each substance and the conditions of manufacture and use must be considered on a case-by-case basis and in many cases where strict controls can be demonstrated, waivers will reduce the testing requirements significantly.

 

The conditions of control must be described in the CSR, communicated and acted upon.  Transported substances (including intermediates), need justified classification for transport and supply and the SDS must include details of the scenarios of use describing explicit conditions for control.  

 


Appendix: List of key studies for each tonnage band and reasons for waivers

 

IUCLID endpoint

Key studies

Comments – waivers / assessments possible

 

Required for all substances

 

The first set of studies are typically necessary for transport classification as a minimum

Section 1

Product characterisation, spectra, analysis etc

Essential.

Required for all registrants, including those involved in joint registrations, SCC intermediates etc

 

4.1

4.2

4.3

4.4

4.7

 

4.11

4.13

4.14

4.12

4.15

4.5

Physical state

Melting point/setting point

Boiling point

Relative density

Water solubility – assess

 

Flash point

Flammability

Explosivity

Autoflammability (self-ignition)

Oxidising properties (solids)

Particle size (granulometry)

 

Essential

DSC analysis usually sufficient.  May indicate purity.

DSC analysis. May indicate purity.

Initial rough check – will determine further testing

Stability in water also needs assessing

 

Essential for substances liquid below 60°C

Essential for substances solid below 60°C

Structure analysis as a minimum

Test if chemical structure or DSC indicates concern

Structure analysis as a minimum

Solids only – indicates need for inhalation toxicity

 

 

 

Phase 2

 

Required for 1 – 10 tonnes

 

(waivers hard to justify and data needed for classification)

The results of the first set are necessary to classify for transport and to ensure control measures in production and use are suitable.  

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 and SDS.

4.6

 

 

4.8

 

4.10

 

 

4.7

 

7.3.1

7.3.2

7.4.1

 

7.6.1

 

7.2

 

6.1.5

 

 

6.1.3

5.2.1

Vapour pressure

 

 

Water solubility

 

Surface tension in water

 

 

Partition coefficient

 

Skin irritation

Eye irritation

Skin sensitisation

 

Bacterial gene mutation (Ames test)

 

Acute toxicity

 

Daphnia immobilisation

 

 

Inhibition to algae

Ready biodegradation

May not be required if boiling point is over 200°C or decomposes.  Important to assess control methods for industrial use.

Normal to assess to 1 mg/l minimum by analysis.

Will impact on further testing.  Check stability.

Only possible to perform satisfactorily if water solubility is above 10 mg/l.  Will impact on partition coefficient.

Key study for environmental fate.  Difficult to assess if surface active

In-vitro.  Animal work only if results negative.

In-vitro.  Animal work only if skin results negative.

Difficult to justify waiver, unless zero exposure.  Modelling is improving to avoid tests.

The first level of mutagenicity assessment – a positive result will lead to further immediate testing

Difficult to justify waiver, unless zero exposure. 

Oral toxicity typically sufficient for classification

Easiest (cheapest) of the short-term environmental effects end-points and difficult to avoid through waivers

Waiver or assessment  justified if ‘zero’ exposure

Even if claiming zero loss to the environment, this is a good study for organic substances.  Waiver difficult.

 

Phase 3

 

Required for 10 – 100 t

 

Depending on Phase 2 studies, waivers are possible in many cases

 

These tests should only be performed after considering results of phase 1 and 2 evaluation.

7.2

 

7.3.1

7.3.2

7.6.1

7.6.1

 

7.5

7.5/7.8

 

5.1.2

 

 

 

6.1.1

6.1.7

 

5.4.1

 

Acute toxicity (inhalation or dermal)

 

Skin irritation

Eye irritation

In vitro cytogenetic (mutagenicity)

In vitro gene mutation, mammal cells

 

Sub-acute toxicity (28 day)

Reproduction screen

 

Abiotic degradation (hydrolysis)

 

 

 

Short term fish toxicity

Bacterial inhibition

 

Adsorption screening

 

Choice of route and need to perform determined by risk of exposure

Animal work not justified.

Animal work not justified.

Choice of method determined by results of bacterial gene mutation (Ames) and waivers hard to justify; read across or other assessments may be justifiable

Routes and methods in view of potential exposure risk.  Modelling and other assessments will reduce justification for new animal testing

Indication of stability should be assessed early in the programme. Only possible to  perform if water solubility is > 10 mg/l. Attempt to identify the degradation products.

Waiver or assessment  justified if ‘zero’ exposure

If any risk of loss to waste water, difficult to justify waiver

Structural evaluation / modelling will suffice if low exposure

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.  Waiver not possible.

 

Phase 4

 

> 100 tonnes or as a result of adverse findings in earlier phases

 

Waivers and assessment must be considered before testing

Animal studies in this section 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

 

4.22

7.6.2

 

7.5

7.8.2

7.8.1

7.7

7.1

 

 

 

 

Solvent stability

Dissociation constant

 

Viscosity

In-vivo mutagenicity

 

Sub-chronic mammalian toxicity

Teratogenicity (rat or rabbit)

One or two generation toxicity studies

Carcinogenicity studies

Toxicokinetic testing - ADME

 

Rarely scientifically valid

Consider if reasonably soluble in water and if structure analysis suggests dissociation.  Check pH.

Only low viscous organic liquids

Only if potential CMR or if very high exposure predicted.

Routes and methods in view of potential exposure risk.  Modelling and other assessments will reduce justification for new animal testing

 

Needs to be considered if high exposure and if results of other studies, for example mutagenicity, suggest a cause for concern.

 

Tier 4

 

Exposure –based studies

 

Only if exposure is predicted

 

 

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.

 

Denehurst Chemical Safety Ltd

Test data requirements for REACH - use of Waivers and alternative to testing

 

REACH registration does not require test data on all endpoints - it is sufficient to provide justified waivers or use justifiable alternatives.  Annex XI of REACH makes this very clear.

 

Waivers for testing or use of non-laboratory data for hazard assessment (Chemical Safety Assessment) must be considered before performing new tests; this is especially important to avoid unnecessary animal testing.

 

Denehurst can provide services to reduce the impact of laboratory testing by assessing potential for waivers or use of non-laboratory data

 

Link to Laboratory Testing    page

 

Link to Animal Testing   page 

 

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Waivers

 

It is not necessary to perform expensive laboratory tests for every endpoint listed.  There is no obligation to perform every test on the lists provided in Annexes VII – X of REACH and within these Annexes, reasons for waivers are provided. Note that Annex XI of REACH describes how waivers and alternatives to testing can be considered.

 

Denehurst can help registrants with the justification for waivers or to help justify read-across and models to avoid excessive laboratory testing. There is an ethical requirement to minimise animal testing and it is important not to be drawn into testing on the basis that 'it is only a couple of thousand Euros for each registrants, so may as well get it done'.  As long as a waiver is thought through and can be justified, the worst that can happen in the future is that ECHA will ask for further justification or perhaps testing; registrants will be given time to do this and while new work is being performed, supply can continue.  

 

 

In the absence of existing data, IUCLID data summary sections provide an opportunity for registrants to request waivers based on

 

 

There are many examples of when waivers will apply, but these will be especially applicable for industrial uses of substances.  The most extreme set of 'waivers' is the supply of intermediates under strictly controlled conditions and in these cases, data requirements are limited; however, if failing to meet 'strictly controlled', but there is still reasonable level of control, reduced testing is possible.