Slovenian arguments against CLP and recommendations for other types of

legislations not CLP

Prof. dr. Damjana Drobne, BF, UL damjana.drobne@bf.uni-lj.si

http://www.bionanoteam.com/

Bionanoteam in international projects:

• EU FP7 NanoValid (2011-2015) • EU FP7 NanoMILE (2013-2017) • H2020 NanoFASE (2015-2019) partner v MSCA-ITN-2015; Marie-Sklodowska-Curie Actions; • H2020 Pandora (2016-2019) • DaNa 2.0, funded by German Federal Ministry of Education and Research

• NanoSafety cluster

Nationa Centres of excelence: •CO NAMASTE •CO Nanocenter

2

What is NanoFuture?

http://www.nanofutures.info/structure

Nano-related platform:

• Communication Projects

• Education Projects

• Finance Projects

• Network Projects

• Safety Projects

• Technical Cooperation Projects

Model tissue and cell studies Blood / blood cells

AChE / enzyme studies

Bacteria / biofilms; in vitro cell cultures

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Model organisms

Engineered nanomaterial mechanisms of interactions with living systems and the environment: a universal framework for safe nanotechnology

Contract Agreement: NMP4-LA-2013-310451 Website: http://www.nanomile.eu

CLH report Proposal for Harmonised Classification and Labelling

Based on Regulation (EC) No 1272/2008 (CLP Regulation),

Annex VI, Part 2

Substance Name: Titanium dioxide EC Number: 236-675-5

CAS Number: 13463-67-7

Index Number: - Contact details for dossier submitter:

ANSES (on behalf of the French MSCA) Ministries of Consumer Affairs, Health, Labour, Ecology and Agriculture,

14 rue Pierre Marie Curie

F-94701 Maisons-Alfort Cedex

reach@anses.fr

Version number: 2 Date: May 2016

EU - TiO2 classification and history

CoRAP Community Rolling Action Plan

In Europe, substances of particular concern are selected for evaluation of risk to human health or the environment and included in the so called Community Rolling Action Plan (CoRAP). Prioritisation of substances shall be risk based.

CoRAP contains details and the indication of the initial grounds for concern for selected substances. Initial grounds for concern for including TiO2 on the CoRap list were: Human health/CMR; Suspected sensitiser; Suspected vPvB; Exposure/Wide dispersive use; Consumer use; Exposure of sensitive populations; Aggregated tonnage. The evaluating member state was France and TiO2 was included on the CoRap list in 2014 (ECHA, 20.3.2013 Community rolling action plan (CoRAP) update covering years 2013, 2014 and 2015; https://echa.europa.eu/documents/10162/13628/corap_2013_en.pdf/543ef605-b03c-452b-83ef-34a286a4e210 )

ECHA

RAC

ANSES

European Commission

The Committee for Risk Assessment (RAC) prepares the opinions of ECHA related to the risks of substances to human health and the environment in the following REACH and CLP processes. The final decisions are taken by the European Commission.

Proposal for Harmonised

Classification and Labelling

Substance TiO2

Thomas Dubouchet France

Proposal for

Harmonised

Classification and

Labelling

Substance TiO2

Problem

Slovenian arguments against CLP and recommendations for other types of

legislations not CLP

TiO2 safety regulation – work done so far by DDrobne and Slovenia

• January 2018 submitted Written comments to CARACAL (presented latter)

• October 2017 Proposal of Task Force for TiO2 safety communication within NanoSafety Cluster

• January 2018 Task Force for TiO2 safety communication approved

• January 2018 published DDrobne Spotlighting CLH report for TiO2: Nano-safety perspective, The Chemical Engineering Journal, DOI10.1016/j.cej.2018.01.007 based on presentation at TiO2 world summit in Alicante, October 2017

Opinion of Slovenian interested parties:

CLP for TiO2 should not be translated into Annex VI.

Argument 1 against direct translated into Annex VI: The CLP report

should follow the Guidance on the Application of the CLP Criteria.

Version 5.0 – July 2017; 3.6. CARCINOGENICITY; 3.6.1. Classification of

substances…and include “the most up-to-date scientific knowledge”.

Suggestion 1: Before final decision is made, the most recent literature

is needed to be considered. We suggested the use a tool developed by

EU funded project GUIDEnano for data quality evaluation.

Opinion of Slovenian interested parties: CLP for TiO2 should not be translated into Annex VI.

Argument 2 against direct translated into Annex VI: TiO2 mode of

adverse action could be described as “particle carcinogenicity” after

inhalation exposure. This type of effect applies to the whole group of

chemicals which referred to as “poorly soluble low toxicity particles”.

Suggestion 2: This data should assist to the prevention of occupational

hazard; dusts at workplace are already monitored; if necessary this

could fall under and regulated under by Safety and health legislation.

•

Opinion of Slovenian interested parties: CLP for TiO2 should not be translated into Annex VI.

Argument 3 against direct translated into Annex VI: TiO2

carcinogenicity is reported toe “Inflammation-Related Carcinogenesis”,

secondary or indirect carcinogenicity which is dose-dependant.

Suggestion 3: CLP classification for Inflammation-Related Carcinogens

is not needed, because they could be regulated by Recommended

exposure limits (RELs).

SOME Grounds for opinion

1. Own research data / General principles of nanobiology / nanotoxicology

2. Recent Guidance on CLH dossiers

1. Own research data

Multifunctional Gadolinium-Doped Mesoporous TiO2 Nanobeads: Photoluminescence, Enhanced Spin Relaxation, and Reactive Oxygen Species Photogeneration, Beneficial for Cancer Diagnosis and Treatment Roghayeh et al. 2017 Small, 13, 1700349

TiO2 interaction with cells - bone cell

A549 lung in vitro model cells

Nanotoxicology. 2017 Apr;11(3):419-429. Harmful at non-cytotoxic concentrations: SiO2-SPIONs affect surfactant metabolism and lamellar body biogenesis in A549 human alveolar epithelial cells. Kononenko V, Erman A, Petan T, Križaj I, Kralj S, Makovec D, Drobne D.

TiO2 nano effect – only shading effect for algae

TiO2 nano – among least biologially potent; effect only on algae

A comparative study

Summary of EU project data!

2. Guidance on CLH dossiers

Classification of a substance as a carcinogen is based on consideration of the strength of the evidence of

available data for classification with considerations of all other relevant information (weight of evidence) being taken

into account as appropriate. Strength of evidence involves the enumeration of tumours in human and animal studies

and determination of their level of statistical significance. A number of other factors need to be considered that

influence the overall likelihood that a substance poses a carcinogenic hazard in humans (weight of evidence

determination). The list of factors for additional consideration is long and requires the most up – to - date scientific

knowledge. It is recognised that, in most cases, expert judgement is necessary to be able to determine the most

appropriate category for classification for carcinogenicity.

• 3.6.2.3. Evaluation of hazard information Annex I: 3.6.2.2.1. Classification as a carcinogen is made on the basis of evidence from reliable and acceptable studies and is intended to be used for substances which have an intrinsic property to cause cancer. The evaluations shall be based on all existing data, peer-reviewed published studies and additional acceptable data.

• Annex I: 3.6.2.2.2. Classification of a substance as a carcinogen is a process that involves two interrelated determinations: evaluations of strength of evidence and consideration of all other relevant information to place substances with human cancer potential into hazard categories.

3.6.2.3.1. Specific considerations for classification

There is a strong link between CLP and the IARC classification criteria. The definitions for

sufficient and limited evidence as defined by IARC are part of the criteria (CLP Annex I, 3.6.2.2.3).

IARC, however, understands the criteria of ‘sufficient’ and ‘limited’ as follows: ‘ It is recognized

that the criteria for these evaluations, described below, cannot encompass all of the factors that

may be relevant to an evaluation of carcinogenicity. In considering all of the relevant scientific data,

the Working G roup may assign the agent to a higher or lower category than a strict interpretation

of these criteria would indicate.’ (IARC 2006 preamble Section 6, Evaluation and rationale). This

sentence emphasises that in certain circumstances expert judgement may overrule the strict

interpretation of the IARC criteria for ‘sufficient’ and ‘limited’. These same limitations apply with the

current criteria in that expert judgement is necessary and can override the strict interpretation of the

definitions.

Way forward 1. Suggestions from the Prague TiO2 expert group meeting to CARACAL /

CEPE based on

2. Plan B: who will do what …. 3. Taking out benefits of all this events for TiO2 for future applications

Thank you for attention!

Additional info

EU NanoSafety Cluster

The EU NanoSafety Cluster maximises the synergies between European-level projects addressing the safety of materials and technologies enabled by the use of nanoparticles. The studied aspects include toxicology, ecotoxicology, exposure assessment, mechanisms of interaction, risk assessment and standardisation. The Cluster is an initiative of the European Commission Directorate-General for Research and Innovation (DG RTD), which sponsors these large projects. Overall, Europe targets safe and sustainable nanomaterials and nanotechnology innovations. Cluster projects contribute to assuring environmental health and safety (EHS) of this Key Enabling Technology.

NANOfutures

• NANOfutures environment is an ETIP European Technology Integrating and Innovation Platform, multi-sectorial, cross-ETP, integrating platform with the objective of connecting and establishing cooperation and representation of Technology Platforms that require nanotechnologies in their industrial sector and products. NANOfutures and its operative branch NANOfutures association act as a “Nano-Hub” by linking JTIs, associations, ETPs with expert groups in a collaborative environment.

• NANOfutures at its base is open to industry, SMEs, NGOs, financial institutions, research institutions, universities and civil society with an involvement from Member States at national and regional level. It is an environment where all these different entities are able to interact and come out with a shared vision on nanotechnology futures. NANOfutures collaborate with the ETPs on the basis of a Memorandum of Understanding.

ANSES

Formal requests to ANSES can come from several sources:

• the government,

• stakeholders represented on its Board of Administrators,

• labour unions.

• The Agency can also issue internal requests when it deems necessary to do so.

ANSES's organisational structure

• The ANSES Board of Administrators includes the five colleges of the Grenelle Environment round table:

• public authorities,

• social partners,

• professional bodies,

• NGOs and non-profit associations,

• elected officials,