# Commission Regulation (EU) 2018/1881 of 3 December 2018 amending Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) as regards Annexes I, III,VI, VII, VIII, IX, X, XI, and XII to address nanoforms of substances (Text with EEA relevance), Division 5: Annex VIII to Regulation (EC) No 1907/2006 is amended as follows:

Extent: E+W+S+N.I.

(a) In the introductory text, the following text is added after the first paragraph:
‘Without prejudice to the information submitted for other forms, any relevant physicochemical, toxicological and ecotoxicological information shall include characterisation of the nanoform tested and test conditions. A justification shall be provided where QSARs are used or evidence is obtained by means other than testing, as well as a description of the range of the characteristics/properties of the nanoforms to which the evidence can be applied.’;
(b) A new section is inserted:
‘7.
INFORMATION ON THE PHYSICOCHEMICAL PROPERTIES OF THE SUBSTANCE
7.14ter.
Further information on physicochemical properties
Only for nanoforms
Further testing for nanoforms covered by the registration shall be considered by the registrant or may be required by the Agency in accordance with Article 41, if there is an indication that specific additional particle properties significantly influence the hazard of or the exposure to those nanoforms.
’;
(c) Subsection 8.5. is replaced by the following:
‘
8.5.
Acute toxicity
8.5.
The study/ies do(es) not generally need to be conducted if:
the substance is classified as corrosive to the skin.
In addition to the oral route (8.5.1.) or to the inhalation route (8.5.2) for nanoforms, for substances other than gases, the information mentioned under 8.5.1. to 8.5.3. shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. If there is only one route of exposure, information for only that route needs to be provided.
’;
(d) Point 8.6.1 is replaced by the following:
‘
8.6.1.
Short-term repeated dose toxicity study (28 days), one species, male and female, most appropriate route of administration, having regard to the likely route of human exposure.
8.6.1.
The short-term toxicity study (28 days) does not need to be conducted if:
a reliable sub-chronic (90 days) or chronic toxicity study is available, provided that an appropriate species, dosage, solvent and route of administration were used, or
where a substance undergoes immediate disintegration and there are sufficient data on the cleavage products, or
relevant human exposure can be excluded in accordance with Annex XI Section 3.
The appropriate route shall be chosen on the following basis:
Testing by the dermal route is appropriate if:
inhalation of the substance is unlikely, and
skin contact in production and/or use is likely, and
the physicochemical and toxicological properties suggest potential for a significant rate of absorption through the skin.
Testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.
For nanoforms toxicokinetics shall be considered including recovery period and, where relevant, lung clearance.
The sub-chronic toxicity study (90 days) (Annex IX, Section 8.6.2) shall be proposed by the registrant if: the frequency and duration of human exposure indicates that a longer term study is appropriate;
and one of the following conditions is met:
other available data indicate that the substance may have a dangerous property that cannot be detected in a short-term toxicity study, or
appropriately designed toxicokinetic studies reveal accumulation of the substance or its metabolites in certain tissues or organs which would possibly remain undetected in a short-term toxicity study but which are liable to result in adverse effects after prolonged exposure.
Further studies shall be proposed by the registrant or may be required by the Agency in accordance with Article 40 or 41 in case of:
failure to identify a NOAEL in the 28 or the 90 days study, unless the reason for the failure to identify a NOAEL is absence of adverse toxic effects, or
toxicity of particular concern (e.g. serious/severe effects), or
indications of an effect for which the available evidence is inadequate for toxicological and/or risk characterisation. In such cases it may also be more appropriate to perform specific toxicological studies that are designed to investigate these effects (e.g. immunotoxicity, neurotoxicity, and in particular for nanoforms indirect genotoxicity), or
the route of exposure used in the initial repeated dose study was inappropriate in relation to the expected route of human exposure and route-to-route extrapolation cannot be made, or
particular concern regarding exposure (e.g. use in consumer products leading to exposure levels which are close to the dose levels at which toxicity to humans may be expected), or
effects shown in substances with a clear relationship in molecular structure with the substance being studied, were not detected in the 28 or the 90 days study.
’;
(e) Subsection 8.8. is replaced by the following:
‘
8.8.
Toxicokinetics
8.8.1.
Assessment of the toxicokinetic behaviour of the substance to the extent that can be derived from the relevant available information.
For nanoforms without high dissolution rate in biological media a toxicokinetics study shall be proposed by the registrant or may be required by the Agency in accordance with Article 40 or 41 in case such an assessment cannot be performed on the basis of relevant available information, including from the study conducted in accordance with 8.6.1.
The choice of the study will depend on the remaining information gaps and the results of the chemical safety assessment.
’;
(f) Point 9.1.3 is replaced by the following:
‘
9.1.3.
Short-term toxicity testing on fish: the registrant may consider long-term toxicity testing instead of short-term.
9.1.3.
The study does not need to be conducted if:
there are mitigating factors indicating that aquatic toxicity is unlikely to occur, for instance the substance is highly insoluble in water or the substance is unlikely to cross biological membranes, or
a long-term aquatic toxicity study on fish is available.
For nanoforms, the study may not be waived on the basis of high insolubility in water alone.
Long-term aquatic toxicity testing as described in Annex IX shall be considered if the chemical safety assessment according to Annex I indicates the need to investigate further effects on aquatic organisms. The choice of the appropriate test(s) will depend on the results of the chemical safety assessment.
The long-term aquatic toxicity study on fish (Annex IX, Section 9.1.6) shall be considered if the substance is poorly water soluble, or for nanoforms if they have low dissolution rate in the relevant test media.
’;
(g) Point 9.1.4. is replaced by the following:
‘
9.1.4.
Activated sludge respiration inhibition testing
9.1.4.
The study does not need to be conducted if:
there is no emission to a sewage treatment plant, or
there are mitigating factors indicating that microbial toxicity is unlikely to occur, for instance the substance is highly insoluble in water, or
the substance is found to be readily biodegradable and the applied test concentrations are in the range of concentrations that can be expected in the influent of a sewage treatment plant.
For nanoforms, the study may not be waived on the basis of high insolubility in water alone.
The study may be replaced by a nitrification inhibition test if available data show that the substance is likely to be an inhibitor of microbial growth or function, in particular nitrifying bacteria.
’;
(h) Subsection 9.2. is replaced by the following:
‘
9.2.
Degradation
9.2.
Further degradation testing shall be considered if the chemical safety assessment according to Annex I indicates the need to investigate further the degradation of the substance.
For nanoforms that are not soluble, nor have high dissolution rate, such test(s) shall consider morphological transformation (e.g. irreversible changes in particle size, shape and surface properties, loss of coating), chemical transformation (e.g. oxidation, reduction) and other abiotic degradation (e.g. photolysis).
The choice of the appropriate test(s) will depend on the results of the chemical safety assessment.
’;
(i) Section 9.2.2 is replaced by the following:
‘
9.2.2.
Abiotic
9.2.2.1.
Hydrolysis as a function of pH.
9.2.2.1.
The study does not need to be conducted if:
the substance is readily biodegradable, or
the substance is highly insoluble in water.
For nanoforms, the study may not be waived on the basis of high insolubility in water alone.
’;
(j) Point 9.3.1. is replaced by the following:
‘
9.3.1.
Adsorption/desorption screening
9.3.1.
The study does not need to be conducted if:
based on the physicochemical properties the substance can be expected to have a low potential for adsorption (e.g. the substance has a low octanol-water partition coefficient), or
the substance and its relevant degradation products decompose rapidly.
For nanoforms, use of any physicochemical property (e.g. octanol-water partition coefficient) as a reason for waiving the study shall include adequate justification of its relevance to low potential for adsorption.
’;

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Source: https://www.legislation.gov.uk/eur/2018/1881/annex/division/5 (the official version)
Page: https://openlegislation.uk/eu-regulation-2018-1881/annex/division-5
Contains public sector information licensed under the Open Government Licence v3.0. Source: legislation.gov.uk, The National Archives.