1 REACH Research

1 REACH Research

1.1 Introduction

Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) is undoubtedly one of the most important European (Regulation???) piece of legislation in last decades. REACH significantly influences whole European market. It affects all spheres of European industry (chemical, pharmaceutical, textile, automobile industry, engineering etc.), importers of chemicals, stakeholders and finally, but most importantly the downstream users.

This new legislation considerably rewrites the current EU chemicals policy and introduces new legal obligations for the industry. There is no other European Regulation which affects the EU Economy as a whole like REACH.

1.2 REACH Evolution

1.2.1 Evolution of European Chemicals Legislation

The idea of regulating chemicals has a long history in the European context. The main European legislations dealing with chemicals regulation are chronologically listed below:

1967 – Directive 67/548/EEC – The first directive concerning the classification, packaging and labelling of dangerous substances. {bv}

1976 – Directive 76/769/EEC – Directive imposing specific restrictions on the marketing and use of a large number of substances. {bv}

1979 – Directive 79/831/EEC – Introduction of Harmonized notification system for all new substances being placed on the market from 1981 onwards. This Directive is amending the Directive 67/548/EEC {bv}

1988 – Directive 88/379/EEC – Introduction of Directive concerning classification and labelling of dangerous preparations (mixtures of two or more substances). {bv}

 1992 – Directive 92/32/EEC – Introduction of Risk assessments for new substances. This Directive is amending the Directive 67/548/EEC {bv}

1993 – Regulation (EEC) No 793/1993 – Regulation concerning the evaluation and control of existing substances, defined as substances placed on the market before 1981. The regulation initiated a process aimed at testing and evaluating these substances in order to assess their potential risks.

Apart from these major pieces of legislation industry sources state that more than 500 additional pieces of Community legislation are related to or influence the EU chemicals industry. {bv} {posledni veta je z European Chemical Industry Council (cefic.org)}

1.2.2 REACH – from naissance to adoption – the policy process

The policy process leading to REACH was initiated by an alliance consisting of the Directorate-General for the Environment, one of the more than 40 Directorates-General and services that make up the European Commission, certain Member States (MS) most notably Austria, Denmark, Finland, The Netherlands and Sweden and a wide range of environmentalist groups, which argued that knowledge of risk and hazards of existing chemicals was insufficient and outdated. These debates gave birth to the review report which was adopted by the European Commission in November 1998 and welcomed by the Council in December 1998. {bv} {br}

In June 1999 after the stakeholders, regulators, scientists, industry, consumer and environmental representatives meeting the Council adopted a set of conclusions for a future strategy calling for new approach to chemicals Regulation and asking the Commission to submit a policy document outlining a strategy. In February 2001 the Commission published a White Paper on a Future Chemicals Policy outlining the REACH proposal, with the aim to harmonize the information requirements for New and Existing Chemicals. The white paper provided the basis for a draft proposal which was debated by the Environmental Council held in June 2001. After successful negotiations European Commission and European Parliament expressed the support for a continuation of the reform process.{bv} {br} {bo}

From October 2001 to February 2002 extensive debates were held within the EU Institutions. This was followed by an internet discussion from May to July 2003. And on the basis of the internet consultation, on 29 October 2003 the European Commission adopted a draft proposal on a new Regulation to assess and regulate chemicals termed REACH (Registration, Evaluation, and Authorisation of CHemicals). {bv} {bo} {bg} {bi}

The first reading of the draft REACH Regulation by the European Parliament took place in November 2005. It led to a number of changes in the original text, producing a list of 430 provisional amendments. {{European Parliament Legislative Resolutions P6_TA(2005)0434 and P6-TA(2005)0435 of 17 November 2005.}} In June 2006, the Council published their proposal for a common position of the Council and the Parliament. In the second reading, held in October 2006, the European Parliament proposed 172 amendments. {bv} {br} {bw}

One month later a compromise package was agreed upon between the Council and the European Parliament and in the December 2006 the Parliament and the Council finally adopted the proposed Regulation. REACH entered into force on 1 June 2007 and is being equally applied in all 27 EU Member States. {bv} {br} {bi} {x2} {q} {x29}

1.3 REACH in Brief

1.3.1 REACH Aim & Objectives

The overall purpose of REACH is to ensure an effective functioning of the contemporary EU market for chemical substances, while ensuring that human health and the environment are not adversely affected by the manufacture or the use of chemicals under reasonably foreseeable conditions. {bg} The REACH concept is aimed to create a single regulatory system for all EU marketed chemicals, it does not differentiate between new (approx. 4,000 chemicals placed on the EU market after 1981 – ELINCS {x5}) and already existing (approx. 100,000 chemicals placed on the EU market before 1981 – EINECS {x3}) chemicals. {x4} Nowadays there are 104,000 chemical substances available on the market of the European Union. Almost a third of them are produced, used or imported in volumes of 1–100 tons per year. Solid data on the human health and ecotoxicological effects are available only for a small percentage of these substances. {bi} {br} {bw} {bm} {i} {b} {q} {x29} -> ctene clanky k tomuto odstavci, ale nepouzite {g} {r} {s} {p}

These untested substances or substances with incomplete toxicological data sheets may pose a risk to the consumers, employees and environment. It is a major purpose of REACH to improve this unsatisfactory situation through the systems of: {bi} {br} {m} {z}

Registration – Data collection on chemical use and toxicity.

Evaluation – Examination by governments of the need for additional testing and regulation of chemicals.

Authorisation of chemicals – Requirements for firms to seek permission to use chemicals of high concern; and

Restrictions or complete ban of certain chemicals that cannot be used safely.{bg}

All these above mentioned elements are discussed in more detail in the Chapter ... ???

Main REACH Aims & Objectives:

Ensure a high level of protection of human health and the environment {Preamble (1)}

Ensure free movement of substances, on their own, in preparations and in articles, while enhancing competitiveness and innovation {Preamble (1)}

Ensure that all chemicals on the EU market, including those produced prior or after 1981, over specified tonnage are covered by REACH

Speed up the processes for testing and risk assessment of chemicals {bv}

Ensure a sustainable development {bv}

The EU expects that by 2020 "chemicals are produced and used in ways that lead to the minimization of significant adverse effect on human health and the environment". {Preamble (4)}

An important REACH objective is "to encourage and in certain cases to ensure that substances of high concern are eventually replaced by less dangerous substances or technologies where suitable economically and technically viable alternatives are available". {Preamble (12)}

Producers, importers and also downstream users will be linked up with the new regulatory system. They are all obliged to ensure the safety of handled substances. {bv}

The substances used and produced for research and development purposes are exempted from the Regulation therefore innovations, product and process oriented research and development should be encouraged. {Preamble (28)} and finally;

Replace, reduce or refine animal testing, with non-testing alternatives such as in vitro and in silico studies etc. {Preamble (47)}

To fulfill all REACH aims and objectives the proper institutional system had to be established. Main responsibilities are carried out by the European Chemical Agency (ECHA) discussed in next chapter.

1.3.2 European Chemicals Agency (ECHA)

Implementation of REACH obviously required the establishment of the complex institutional system, with a regulatory agency, the European Chemicals Agency (ECHA), at its center. ECHA is based in Helsinki, Finland. {bv} ECHA will be employing around 500 officials and chemical safety experts, as such being the largest Agency within the European Union, having annual budget in the region of EUR 70 million for 2009 {x11}. {x7} {bv} {x29}

ECHA defines its mission as: {x10}

Manage the registration, evaluation, authorisation and restriction processes for chemical substances to ensure consistency across the European Union.

Manage and carry out technical, scientific and administrative aspects of REACH.

Ensure consistency at Community level in relation to these aspects.

Provide the Member States and the institutions of the Community with the best possible scientific and technical advice on questions relating to chemicals which fall under REACH.

Manage IT based guidance documents, tools and data bases.

Support national helpdesk and run a helpdesk for registrants.

Make information on chemicals publicly accessible. {x10}

Since ECHA is the EU's largest Agency, it has very complex organization structure as listed below and shown in the Fig 323. {x8}

The European Chemicals Agency comprises:

A Management Board, responsible for adopting the financial planning, work programme, annual reporting.

An Executive Director, the legal representative of the Agency, responsible for the day to day management and administration of the Agency, including responsibility over its finances. The Executive Director reports to the Management Board.

A Secretariat to support the Committees and Forum and undertake work on registration and evaluation processes as well as preparation of guidance, maintenance of databases and provision of information.

A Member State Committee to resolve differences of opinion on draft decisions proposed by the Agency or Member States and make proposals for identification of substances of very high concern.

A Risk Assessment Committee to prepare opinions on evaluation, on applications for authorisation, on proposals for restrictions and on classification and labelling.

A Committee for Socio-economic Analysis to prepare opinions on applications for authorisation, on proposals for restrictions and on questions relating to the socio-economic impact of proposed legislative action.

A Forum on enforcement matters to coordinate a network of Member States' competent authorities responsible for enforcement.

A Board of Appeal to decide on appeals against decisions taken by the Agency. {x8}

Figure 232/....

1.3.3 Animal Testing

REACH foresees to test approx. 30,000 chemicals until 2018. These are the chemicals used, produced or imported in quantities greater than 1 tonne/year on EU market. To perform all tests on toxicity, ecotoxicity etc. a great number of animals will be needed. First estimations from 2005 were rather catastrophic, they assumed that approx. 7.5–45 million experimental animals, mainly rats and mice, will be needed within the first 15 years. {bi} In further estimations the number of testing animals decreased to 3.9 million (including 2.6 million vertebrates). {bm} According to these numbers British news server politics.co.uk entitled REACH as “world’s biggest ever animal testing programme” {x13}.

In the European Union (EU), the use of non-testing methods, and in particular in silico methods, is explicitly encouraged and even required in the REACH Regulation. There is a great effort to identify the presence or absence of hazardous properties of the substance while at the same time minimizing the costs of experimental tests and the use of vertebrate animals. {bn} {c} {d} These alternative methods may provide significant information about the basic physicochemical properties of chemicals as well as their ecological and human health effects. {bn} {bc} {f} {j} {o} {y} -> ctene clanky k tomuto odstavci, ale nepouzite {bt} {bu} {bb} {k} {l}

1.3.4 Non-testing methods

Main role in enforcing the reduction of animal tests plays the European Centre for the Validation of Alternative Methods (ECVAM) created by the Communication from the Commission to the Council and the Parliament in October 1991 {x14}. ECVAM requires that the Commission and the Member States actively support the development, validation and acceptance of methods which could reduce, refine or replace the use of laboratory animals.

ECVAM defines its duties as: {x15}

1. To coordinate the validation of alternative test methods at the European Union level.
2. To act as a focal point for the exchange of information on the development of alternative test methods.
3. To set up, maintain and manage a data base on alternative procedures.
4. To promote dialogue between legislators, industries, biomedical scientists, consumer organisations and animal welfare groups, with a view to the development, validation and international recognition of alternative test methods. {x15}

There are several REACH preferred non-testing methods where the most significant and used are Qualitative/Quantitative Structure–Activity Relationship (Q)SAR, Activity – Activity Relationships (AARs), Quantitative Structure–Activity–Activity Relationships (QSAAR) or the In vitro tests {bn} -> ctene clanky k tomuto odstavci, ale nepouzite {u} {x} {v}

All these non-testing methods are based on the premise that their chemical properties (including biological activities) depend on their intrinsic nature and can be directly predicted from their molecular structure and inferred from the properties of similar compounds whose activities are known. {bn} {c} {d} Fig.1 shows the workflow for the use of non-testing data in chemical assessment. {bn} (Q)SAR and in vitro methods are discussed in more detail in the following chapters.

Figure 1: Workflow for the use of non-testing data in chemical assessment. {bn}

1.3.4.1 (Q)SAR

(Q)SAR is a general term making reference either to Qualitative (SAR) or Quantitative (QSAR) Structure–Activity Relationship. SARs are theoretical models that can be used to predict in a qualitative manner the physicochemical, biological (e.g. toxicological) and fate properties of molecules from knowledge of chemical structure. More specifically, an SAR is a qualitative relationship (i.e. association) between a molecular (sub)structure and the presence or absence of a given biological activity, or the capacity to modulate a biological activity imported by another substructure. {bn}

A QSAR is a quantitative relationship between a biological activity (e.g. toxicity) and one or more molecular descriptors that are used to predict the activity. A molecular descriptor is a structural or physicochemical property of a molecule, or part of a molecule, which specifies a particular characteristic of the molecule and is used as an independent variable in a QSAR. {bn}

Under REACH, it is possible to use data from (Q)SAR models instead of experimental data if each of four main conditions is fulfilled:

1. the model used is shown to be scientifically valid;
2. the model used is applicable to the chemical of interest;
3. the prediction (result) is relevant for the regulatory purpose and
4. appropriate documentation on the method and result is given. {bn}

1.3.4.2 In vitro

Another alternative non-testing method is in vitro (in glass or in a test tube), the opposite ofin vivo (test in a living organism). {x16} In vitro, the REACH preferred tests, are proposed as complementary to whole-animal testing (in vivo tests). {k} {n} {h}

There still exists a great discussion whether in vitro can completely replace in vivo tests and the answer is “no” or more precisely “not yet” according to the following reasons:

“In inhalation toxicology, there is no universal or accepted test system to replace inhalation exposure studies.” {bl}

“It is unrealistic to think that there might be a single in vitro bioassay that could represent the varied population of cells of the respiratory tract.” {bl}

“In vitro systems are not yet capable of fully replacing in vivo testing to predict neurotoxicity, especially when the site of action is unclear or unknown. However, at this stage of methods development and validation in vitro techniques can provide valuable information that complement established in vivo neurotoxicity testing strategies as it was proposed for developmental neurotoxicity.” {bm}

“In vitro cytotoxicity assays fail to predict acute toxicity in 20–30% of the tested chemicals.” {bm}

ctene clanky k tomuto odstavci, ale nepouzite -> {be}

1.3.4.3 Non-testing methods conclusion

The use of non-testing methods, especially under REACH, is inevitable. Without these methods millions of additional testing animals (including vertebrates) would be killed and catastrophic scenarios of testing up to 45 million animals would be fulfilled. But there is always a risk of getting incorrect results from these alternative methods, because none of these methods can completely replace the in vivo test.

1.4 REACH Procedures

According to the European Commission the aim of REACH is “to improve the protection of human health and the environment through the better and earlier identification of the intrinsic properties of chemical substances. At the same time, innovative capability and competitiveness of the EU chemicals industry should be enhanced.” {x17} To fulfill this objective REACH implements four main, already mentioned, procedures – Registration, Evaluation, Authorisation and Restriction of chemicals.

REACH covers all substances on their own, in preparations and in some articles that are placed on the EU market in quantities above 1 tonne per year. Substances used for the scientific research and development purposes are exempted from the Regulation as well as the producers or importers handling quantities of less than one tonne per year of a specific substance. {bv} {x6} {q} {bw} {bi} {x29}

It is estimated that more than 30,000 substances will be tested under REACH. Tab 2. shows the four main groups of substances according to their tonnage. {z} ctene clanky k tomuto odstavci, ale nepouzite -> {m} {b} {p}

Tonnes per annum / Number of substances / REACH annex
1-10 / 17,500 / Annex VII
10-100 / 4977 / Annex VIIII
100-1000 / 2641 / Annexes IX
> 1000 / 7204 / Annex X

Table 2.: Overview of tonnage ... ?

The European Chemicals Bureau (ECB) {x18} analyzed the data received from industry on the properties of their substances, produced in more than 1000 tonnes/year. These substances are called High Production Volume Chemicals (HPVC) and there is significant lack of complete information about the majority (97%) of them. The information about HPVC is listed below: {x28}

3% – Tested

11% – Minimal data – only a base set

65% – Very little data – less than a base set

21% – No data {x28}

1.4.1 Registration

The Registration can be understood as a process of data collection on chemical use and toxicity. Importers and manufacturers of chemicals must submit a registration for all chemicals produced in quantities larger than 1 tonne/year per producer {bg}. Before REACH entered into force, substances on the EU market prior 1981 were not subjected to any mandatory testing or review. Since REACH is in force, no distinction is made between substances marketed before and after 1981. All chemical substances on the EU market over particular threshold must be subjected to the registration. {bg} {m} {e} {x29}