Key Points for Chemical Safety Assessment in
REACH (Draft)

This document was prepared by the Chemicals Evaluation and Research Institute, Japan (CERI) as“Information Gathering / Reporting Tasks Regarding Chemical Safety Assessment in REACH in2008” founded by the Ministry of the Environment

Introduction
The new European chemical regulation, REACH (Registration, Evaluation, Authorisation and Restriction ofChemicals), was enforced on June 1, 2007, and thereafter, pre-registration for REACH took place during theperiod between June and December 2008. Upon registration for REACH, the registering companies themselves
need to conduct hazard and exposure assessments and submit a set of documents, which show that the risks areadequately controlled, to ECHA (European Chemicals Agency) as part of the documents required for registration.
In REACH, “manufacturers” and “importers” of substances on their own or in preparation in Europe which arecovered by REACH are required to register these substances. For the registration, they are required to conduct
Chemical Safety Assessment (CSA). The “Downstream Users (DUs),” who are at the downstream, must informthe registering manufacturers or importers (M/I) about the use1 / exposure information required for CSA. If theusage in DUs is not included in CSA conducted by the upstream M/I, DUs need to conduct CSA by themselves.
Although REACH is applied only to legal entities (including individuals) within Europe, Japanese companies
should take this system into consideration as well since exporters (those who export chemical substances
themselves and various materials which contain these substances to Europe from outside Europe) would need toprovide European importers the information required by REACH regulation in their business. In addition, eventhose who do not export directly to Europe or those who provide substances, preparations or products indirectly or
directly to exporters to Europe may also be required to submit information. The failure to submit the necessary
information to the authority or to put it on the supply chain in Europe may affect the marketing of the substance or
any products containing the substance in Europe. For this reason, all associated companies outside Europe,
including Japanese companies, are required to pay attention and take necessary action to this system in theirbusiness.
With regard to preparation of registration documents for REACH, a large number of guidance documents havebeen prepared and published mainly by ECHA, however, these documents contain a large amount of highly
specialized contents. Of all guidance documents for REACH registration, the guidance document associated with
CSA2 is considered the most important for safety assessment of the chemical substance to be registered. There areconcise and detailed versions for the CSA guidance documents. Of these, the concise version is translated andreleased to the public by Ministry of the Environment of Japan3.
This document was first prepared to provide additional information that would promote understanding of CSA in
REACH for those involved in risk assessment / management-associated tasks to conduct CSA mainly based on
CSA guidance documents. In addition, explanatory topics regarding terms and ideas specific to REACH are newly
added to the content. This document however dose not cover the entire content described in the guidance
document. Therefore, it is recommended to refer to the original guidance documents upon the actual conduct of
CSA.

1

The term “use” is defined by the REACH as follows, “use: means any processing, formulation, consumption, storage, keeping,treatment, filling into containers, transfer from one container to another”. (REACH article 3(24)). It is noted that transfer from acontainer to another, storage and keeping are also included into “use” in REACH.
2“Guidance on information requirements and chemical safety assessment”; published in May 2008.
This includes concise guidance (Part A - Part G) and in-depth guidance (R.2 - R.20).
The original document can be downloaded from the website below.
http://reach.jrc.it/docs/guidance_document/information_requirements_en.htm
3
The Japanese translation of the guidance document can be downloaded from the website of Network for Strategic Response on
International Chemical Management below.
http://www.chemical-net.info/regulation.html

1Upon preparation of this document, a technical committee, which consists of the following members and thesecretariat, was established, and the contents and structures of this document were discussed.

Technical Committee Member （Honorific titles are omitted）
Name
Yasunobu AOKI
(Chair person）

Toshiaki ICHIKAWA

Katsuya SATO

Fumiaki SHONO

OfficeSection Head, Health Risk Research Section
Research Center for Environmental Risk
National Institute for Environmental Studies
Chief Engineer, Corporate Environmental Policy Division
Hitachi, Ltd.
Professor, Department of Science and Engineering
CHUO UNIVERSITY
Vice Secretary-General, REACH Task ForceJapan Chemical Industry Association
Senior Researcher, Exposure Assessment Research Section

Norihisa TATARAZAKO

Research Center for Environmental Risk
National Institute for Environmental Studies
Secretariat

Chisumi ETO
Toshiki Nozaka
Kazumi KAWAHARA

Chemicals Assessment and Research Center
Chemicals Evaluation and Research Institute (CERI)

2

Contents
1

Introduction

1.

Chemical Safety Assessment (CSA), Chemical Safety Report (CSR), and Safety Data Sheet (SDS) in REACH
4

2.

An Overview of Guidance Document on Information Requirements and Chemical Safety Assessment

8

3.

Hazard Assessment

10

4.

PBT Assessment

18

5.

Exposure Assessment

21

6.

Risk Characterisation

34

7.

Chemical Safety Report (CSR)

37

8.

Safety Data Sheet (SDS)

39

Topic-1：Viewpoints of Risk Assessment in REACH

7

Topic-2：What is Weight of Evidence ?

11

Topic-3：Derived Non-Effect Level (DNEL) and Predicted Non-Effect Concentration (PNEC) in REACH

13

Topic-4：Quantitative/Qualitative approach in hazard assessment

14

Topic-5：Category Approach

16

Topic-6：What is Klimisch Code ? An Index for Reliability Assessment of Hazard Data

17

Topic-7：Uncertainty Analysis

36

Topic-8：Preparation of CSR Format Using Plug-in Software to IUCLID 5

38

List of Abbreviations

40

Useful Links

41

3

1. Chemical Safety Assessment (CSA), Chemical Safety Report (CSR), andSafety Data Sheet (SDS) in REACH
1.1 CSA, CSR and SDS in REACH
The goal of the chemical Safety Assessment (CSA) is not to establish whether or not there is a risk, but to identify
and describe the conditions under which the risks are controlled.
Upon REACH registration, a Registration Dossier needs to be prepared for each substance. The Registration
Dossier contains the following two documents.
-

Technical Dossier: Required for all substances (more than 1 ton / year) which require REACH registration.
CSR (Chemical Safety Report): Required for a substance of 10 tons / year. This is a document which contains
the results of CSA and the safety assessment (where operational conditions under which risks are adequately
controlled are described).

The Technical Dossier must be prepared by using a specific software called “IUCLID5 (International Uniform
Chemical Information Database)”4. Alternatively, CSR is independent of the Technical Dossier, and there is no
specific software required for the preparation of the document.
The purpose of safety assessment of a chemical substance in REACH registration is to establish safety conditions
associated with the manufacturing and use of the substance at any stage of the lifecycle. The registrant who
manufacturers or imports chemical substances more than 10 tons / year is to conduct CSA and submit a document,
which includes the results of CSA and its evaluation, to European Chemicals Agency (ECHA) as CSR along with
the Technical Dossier.
Usually, CSA is conducted by the registering manufacturer or importer (M/I), but the registrant is required toevaluate if the risks associated with not only their own manufacturing / use but also processing / use of thesubstance by DUs (Downstream Users) in the supply chain are appropriately controlled.
The use of the substance recognized by M/I and specified in CSR is called “Identified Use (IU).” The “IU” isdefined as “use of a substance on its own or in a preparation, that is intended by an actor in the supply chain” in
REACH (Article 3 (26)). An assessment should be made if the risks are appropriately controlled in the use of thesubstance or in a preparation, and the results of the assessment need to be documented in SDS (Safety Data Sheet)along with hazard information of the substance and communicated to DUs.
Besides this, there are other types of CSAs e.g. when DUs use a chemical substance other than IU, etc., or CSA
which is associated with application for authorisation of a substance of very high concern. The procedures
required in these cases are described in the CSA Concise Guidance Document Part A.4.

4

The software IUCLID5, which is used to prepare the Technical Dossier can be downloaded from the website below:
http://iuclid.echa.europa.eu/

41.2 An Overview of CSA
CSA is required for a substance manufactured or imported in a quantity of 10 tonnes or more per year in EU
region and is normally proceeds in following steps.
Step-1：
Step-2：

Step-3：
Step-4：

Step-5：

Collection and generation of available and required information on intrinsic
properties（See CSA Concise Guidance Document Part A）
Human health hazard assessment; including classification and derivation of derived
no effect levels（DNELs）(where that is not possible other indications of the potencyof the substance) (See CSA Concise Guidance Document Part B.7.1 and CSA
in-depth Guidance Document R.8)
Physicochemical hazard assessment; including classification (see CSA In-depth
Guidance Document R.9)
Environmental hazard assessment; including classification and derivation ofpredicted no effect concentration (PNECs) (See CSA Concise Guidance Document
B.7.2 and CSA In-depth Guidance Document R.10)
PBT（Persistent, Bioaccumulative and Toxic） and vPvB（Very Persistent and Very
Bioaccumulative） Assessment (See CSA Concise Guidance Document Part C, CSA
In-depth Guidance Document R.11）

If, as a result of the hazard assessment, it is found that a substance meets the criteria for classification as
dangerous according to the criteria of Directive 67/548/EEC5 or 1999/45/EC, or is a PBT or vPvB substances,then exposure assessment and subsequent risk characterisation is required (See Figure 1-1). If a substance does
not meet the criteria for classification as hazardous substances or is not a PBT and vPvB substance following steps
are not required.
Step-6：
Step-7：

Exposure assessment (covering development of exposure scenarios and exposure
estimation (See CSA Concise Guidance Document Part D)
Risk Characterization (See Concise Guidance Document Part E)

CSA iterations may be needed depending on a result of the risk characterisation.
Step-8：Potential CSA iteration (See Concise Guidance Document Part A)

Figure 1-1 shows an overview of CSA.

5

Directive 67/548/EEC can be found at ECB’s (ECB：European Chemical Bureau）web site below. It should be noted that thisDirective will be repealed and replaced with GHS （Globally Harmonised System of Classification and Labelling of Chemicals） by
2015.
http://ecb.jrc.ec.europa.eu/classification-labelling/5

Information：available ⇔ required （Step-1）

Exposure Assessment (EA) （Step-6）

Hazard Assessment（HA）（Steps-2-4）nyDangerous or
PBT

Stop

Risk Characterisation（RC）(Step-7)

Step-5Iteration (Step-8)

Document
in CSRyn

Risk
controlled?

Communicate ES
via eSDS

Each step correspond to section 1.2

Figure 1-1 Overview of CSA

1.3 Items Required for Registration
The items required for REACH registration are described below.
CSR

Technical Dossier・ Identity of the registrant
・ Identify the substance・ Information on manufacturing and use of
the substance・ Hazard classification and labelling・ Guidance on its safe use・ (Robust) Summary of substance specifichazards
・ Study plan (if necessary)・ Information regarding exposure・ Hazard, PBT, vPvB assessment
If it is dangerous (classified) or PBT, vPvB
substance, the following are added.
・ Exposure Scenario (ES)・ Estimation of the amount of exposure
・ Risk characterisation

1.4 Output of CSA
Normally following outputs are required in CSA.
1) Available information for the hazard assessment, classification and labelling, PBT/vPvB assessment andthe derivation of the hazard threshold levels for human health and the environment2) Where the assessment shows that the substance meets the classification criteria or PBT/vPvB criteria,
6identification the conditions under which the risks can be adequately controlled; i.e. exposure scenarios(ES)3) Assessment results (described in CSR）
4) When ES are developed, the company and downstream users shall implement the conditions of use
where risks adequately controlled. The information on the identified use is not only described in CSR but
also its summary is attached in the extended safety data sheet (eSDS)6 and is communicated further
downstream users via the supply chain (See Chapter 8: Safety Data Sheet, p39, and CSA Concise
Guidance Document Part G).

Topic-1
Viewpoints of risk assessment in REACH“Risk assessment” is a concept which appears in REACH text, but its definition is not provided
there. The “risk” is generally expressed by the product of hazardous properties intrinsic to thesubstance, and the amount of exposure to humans or living organisms determined by the amountmanufactured or the condition of use. However, in REACH, the concepts of “risk characterisation”
and “control of risk” which are the main concepts in CSA, are clearly described rather than giving ageneral definition of “risk.” Although the hazardous properties are inherent in each substance, risks
can be reduced by changing the condition of use consisting of the operation conditions or Risk
Management Measure (RMMs), including the use patterns.
In CSA Guidance Document, it is defined that “the goal of the assessment is not to establish whether
or not there is a risk, but identify and describe the conditions under which risks are controlled”. The
risk characterisation is a process to confirm such conditions and performed by 1) collecting hazard
information and deriving the hazard descriptor (DNEL, PNEC, etc.) for the risk characterisation, 2)
exposure assessment, and by 3) comparing the amount of exposure to the hazard descriptor. As aresult, it is considered that “the risk is controlled” when the amount of exposure does not exceed thehazard descriptor.
Therefore, for a substance of which the level of the hazard descriptor is very small (highly
hazardous substance), it may be required to take some measures to reduce the amount of exposurecompared to a substance with high hazard descriptor level. In addition, for substances with highhazard descriptor level (low hazard substances), risk assessment can be discontinued at the point
where the risk control is confirmed in comparison with the amount of exposure which is predictable
in a worst case scenario, without performing detailed and complicated exposure assessment.
Furthermore, a substance which is considered as low-hazard (unclassified) according to the resultsof hazard assessment and do not correspond to PBT / vPvB substance is judged as low risk, andquantitative exposure assessment or risk characterisation is not required regardless of the
manufactured or imported volume.
For those substances having a property of carcinogenicity, mutagenicity and reproductive toxicity(CMR) or PBT/vPvB (See Chapter 4: PBT Assessment), or possibly having similar properties which
are highly concern (e.g. endocrine disruption) is specified as Substances of Very High Concern(SVHCs) and is subject to the authorisation. The SVHCs in articles are required to notify all users of
the substance. Some substances prioritised for the authorisation from the SVHCs shall be prohibitedto use as substances themselves or substances in the mixture and to incorporated into articles unlessthe user of the substances or the suppliers for the user would submit the application for authorisation
for such use(s) of the substance(s) and to be granted authorisation to such use(s) by ECHA. Detailed
guidance document “Guidance for the preparation of an Annex XV dossier on the identification ofsubstances of very high concern” is published by ECHA.

6

Information on identified use, operational conditions and risk management measures (RMMs) under which risks are adequately
controlled is described in usual MSDS and is used to communicate to downstream users. This MSDS is called as extended SDS(eSDS) in REACH.

7

2. An Overview of Guidance Document on Information Requirements andChemical Safety Assessment
European Chemicals Agency (ECHA) has prepared and published a document including the following contents as
guidance on information requirements and CSA (hereinafter referred to as CSA Guidance Document).
・ Collection of information regarding intrinsic properties of a substance to be registered underREACH
・ Evaluation of information required in REACH
・ Identification of data gap (lack of data required for registration)
・ Acquisition of additional information to fulfil the data gap
This CSA Guidance Document is prepared to support registrants to conduct CSA appropriately and to record theassessment results in CSR. The CSA Guidance Document consists of the Concise Guidance Document (Part A –Part G) and the In-depth Guidance Document (R.2 – R.20) (Figure 2-1).

－Concise Guidance－－In Depth Guidance－
R.2: Framework for generation of information on
intrinsic properties
R.3: Information gathering,
R.4: Evaluation of available information
R.5: Adaptation of information requirements
R.6: QSARs and grouping chemicals
R.7: Endpoint specific guidance

A: Introduction

R.8:Characterisation of dose-response for humanhealth
R.9: Physico-chemical hazards
R.10: Characterisation of dose-response for theenvironment

B: Hazard Assessment

R.11: PBT/vPvB Assessment

C: PBT/vPvB Assessment

R.12: Description of Uses
D: Exposure Assessment

R.13: Conditions of Use (RMM,OC）
R.14: Occupational exposure estimation
R.15: Consumer exposure estimation
R.16: Environmental exposure estimation
R.17: Estimation of exposure from article
R.18: Estimation of exposure from waste life stage

E: Risk Characterisation

R.19: Uncertain Analysis

F: Chemical Safety Report
R.20: Explanation of Terms
G: Extension of the SDS

Figure 2-1 Structure of the Guidance Document

Main contents in the concise guidance documents are shown in table 2-1.

8

Table 2-1 Overview of the Concise Guidance
Structure
Part A
Introduction

Part B
Hazard Assessment

Part CPBT Assessment

Part D
Exposure Scenario
Building

Part E
Risk Characterisation

Part F
CSR and its Template

Part G
Extending the SDS

Summary
Overview and summary of the CSA and concise guidance documents Part B to Part G.
Part B contains concise guidance on the hazard assessment. Part B covers theinformation requirements under REACH, including information gathering, non-testing
approaches and the so-called ‘integrated testing strategies’ for generating the relevant
and required information on each endpoint. It also provides concise guidance on how
to characterise hazards, including where possible derivation of DNELs and PNECs.
Each sections in Part B corresponds to the more in-depth guidance contained in
Chapters R.2 to R.10.
Part C contains the concise guidance on how to assess whether or not a substance is
PBT or vPvB substance. In-depth guidance on the PBT and vPvB assessment iscovered in Chapter R.11.
Part D details how to develop exposure scenarios and related exposure estimation. Part
D contains in-depth workflows on how to identify uses in the supply chain, how todevelop exposure scenarios and finalise them based on the iterations necessary forcontrolling risks. Part D provides in particular how to describe uses, how to collectinformation on operational conditions and risk management measures, and how tocarry out exposure estimates. In-depth guidance on the exposure scenario is describedin in-depth guidance R.12 to R.18.
Part E contains the guidance on the risk characterisation. In the risk characterisation,
information on hazard and exposure is combined in the risk characterisation ratio(RCR) or in qualitative risk characterisation. The uncertain analysis is further in-depth
in in-depth guidance R.19.
Part F details the format and requirements for preparing the chemical safety report,
which documents the results of the entire chemical safety assessment. Part F details
subsections to the main headlines and provides guidance on how to present theoutcome of the CSA. It also explains how to use the CSR template.
Part G contains the guidance on preparing the extensions to the safety data sheet(SDS). This contains information on how the exposure scenario is communicated andimplemented in the supply chain. In an appendix to Part G it is exemplified how DUs
may scale exposure scenarios according to their conditions of use. It also includes anumber of approaches how to process at DUs level information received with theextended safety data sheets and how to communicate to further down.

93. Hazard Assessment
3.1 The Basic Method of Hazard Assessment
The procedures for hazard assessment in REACH are described in the following four steps in the CSA Concise
Guidance Document.
Step-1:Gather and share existing information (See CSA Concise Guidance Document Part b.4 to B.6)
The registrant must collect all physicochemical, toxicological, ecotoxicological and exposure
information that is relevant and available regardless at the specific tonnage level. Animal testing data
shall share with registrants of the same substance and other information as well. For phase-in substances,
Substance Information Exchange Forum (SIEF) will play as such role.
Step-2:

Consider information needs (See CSA in-depth Guidance Document R.2, R.5, R.7, REACH
Article Annexes VII to X)
The registrant needs to identify the standard information requirements according to tonnage
manufactures or imports. In this stage waving of the information requirements and additionally required
information should also be confirmed.

Step-3:
Identify information gaps （See CSA In-depth Guidance Document R.7）
In step-3, the registrant compares the information needs for the substance identified in step 2 withthe reliable and relevant information already available as identified in step 1. Where the REACH
regulatory requirements cannot be fulfilled with relevant and available information, data should beobtained in accordance with the procedures of step 4.
Step 4:Generate new information or propose a testing strategy (See Concise Guidance Document B.6,
CSA in-depth Guidance Document R.7)
When a data gap has been identified in step 3 for information requirements, the registrant needs todevelop a testing proposal and include it in the registration dossier. While waiting for the results of thistesting, the registrant should apply interim safety operational conditions (OCs) and risk management
measures (RMM) to own manufacture or use, and communicate such information to down stream users.

3.2 Exemption from or Addition to the Information Requirements
Although information requirements are determined in REACH according to the manufactured or imported volumeof the substance, it is also mentioned that an additional study is not necessarily required if the conditions
described below are fulfilled. However, if information is available, it has to be reported in the Registration Dossier
regardless of the following conditions. Moreover, information which is not included in the requirements may berequested according to the exposure condition. Contrary testing may possibly be exempted depending on the
exposure conditions (See CSA In-depth Guidance Document R-5 for details).

1) Testing does not appear scientifically necessary
Existing data, Weight of Evidence approach (See Topic-2), non-testing methods and in vitro
methods may provide information that may be judged to be valid, reliable and adequate for theidentified purpose (classification and labelling, PBT assessment, and/or risk assessment).

2) Testing is technically not possible
It is described in REACH that testing for a specific endpoint may be omitted if it is technically notpossible to conduct the study as a consequence of the properties of a substance, e.g. volatile, lowwater solubility, reactivity. However, justifiable such reasons should be stated in the registration
dossier.
3) Substance-tailored exposure driven waiving or testing10

In certain situations, the exposure pattern of the substance to be registered may justify adaptation of thetesting strategy leading to omission, triggering, replacement or modification of the studies required forcompliance with REACH. For example, in case a specific exposure route (oral, inhalation, dermal, etc)
is not expected at an ES, and adding testing data of such administration route does not affect the risk
characterisation, it may be decided that conducting the study is not necessary.

Topic-2
What is Weight of Evidence?
（See CSA Concise Guidance Document Part B.4 for details）
In recent years, the term “Weight of Evidence” has been seen in documents not limiting in guidance
documents on REACH but also other documents. Although the term “Weight of Evidence” is notdefined strictly, it can be generally considered as the following.
If multiple study data are available in the same endpoint and the level of hazard varies, one data has
priority over the others to be used in the risk assessment according to the applicability, reliability, andvalidity, etc. of the data. In order to judge this, “Weight of Evidence” is used. In other case that all data
indicate the same direction but none of which is in itself sufficient to draw a conclusion, then only
together they give enough weight to allow a conclusion.
The criteria to judge heaviness or lightness of evidence include the following.
1) Applicability: The types or the results of the study agree with the purpose of assessment (itcan be thought that the longer study (administration) period, the higher the applicability ofthe data in the assessment for chronic effects).
2) Reliability: The criteria to judge reliability include the following conditions: the study musthave been conducted in accordance with international study methods, such as OECD Test
Guideline, etc., as well as GLP criteria, and the results of the study should be relatively
consistent. In addition, Klimisch Code, which is described in Topic-6, is often used as
quantitative criteria to judge reliability.
3) Validity: The equivalence is usefulness of data. For instance, usefulness is considered higher
with in vivo study data than with in vitro study data.
The weight of evidence of available data is evaluated based on the above mentioned points, but thisrequires experts’ judgement.

3.3

Human Health Hazard Assessment

3.3.1

Hazard data for human healthFor human health hazard assessment, the following effects need to be considered.
・
・
・
・
・

Toxicokinetics, absorption, distribution, metabolism and excretion
Acute effects (acute toxicity, irritation and corrosivity）
Sensitisation
Repeated dose toxicity, andCMR effects （carcinogenicity, mutagenicity and reproductive toxicity）

In REACH, hazard assessment for humans requires calculation of Derived Non-Effect Level (DNEL), and for this,No Observed Adverse Effect Level (NOAEL) or Lowest Observed Adverse Effect Level (LOAEL) needs to beobtained from the study data.
Furthermore, data on exposure characteristics (See Chapter 5 Exposure Assessment in this document) andphysiochemical properties of the chemical substance need to be collected as well (See CSA Concise GuidanceDocument B.7).
11

3.3.2

Calculation of Derived No-Effect Level (DNEL)

In hazard assessment for humans in REACH, DNEL needs to be calculated for each route of exposure caused by
the identified use (IU). Therefore, when more than one route of exposure has been identified, DNEL and DNEL of
combined exposures need to be calculated by using a dose descriptor7 for each route of exposure (See Topic-3).
In order to address differences between animal testing data and real human exposure situations, it is proposed touse assessment factors (AF) considering following uncertainties.
・ The uncertainty arising from the variability in the experimental data and from intra- and interspecies variation
・ The nature and severity of the effect;
・ The uncertainty arising from the variability of the frequency of the exposure and variation of the
exposed concentration.
Taking into account the above factors, unusually DNEL can be derived from NOAEL using several AFs.

DNEL =

NOAEL
NOAEL
=
AF1 × AF 2 × ⋅ ⋅ ⋅ AFn OverallAF

See CAS In-depth Guidance Document R-8 for the actual AF values and the method of calculation to obtain
DENL.
Figure 3-1 shows the workflow of the deviation of DNEL and the risk characterisation for human health.

Set dose descriptors (e.g. NOAEL) based on the available information and toxicological studies

If necessary, modify the dose descriptor to the correct starting point
Calculate the overall assessment factors based on all the uncertainties involved in the assessment
Develop DNEL by dividing the dose descriptor with the overall assessment factor
Conduct risk characterisation (RC) for each separate exposure route (and long-term/acute/different
populations) by dividing exposure with the relevant DNEL; control of risk requires a ratio < 1

When the risk for each separate exposure route is controlled, if appropriate, conduct RC for
simultaneous exposure via all route of exposure
Figure 3-1 Overview of the human health risk assessment for threshold endpoints

7

Dose descriptor: This is an indicator for toxicity obtained from a toxicity / Eco-toxicity study or other related data and is usually adose required to induce specific adverse effects (e.g., lethal dose 50) or the maximum concentration which do not induce adverse
effects (e.g., NOAEL). The dose descriptor becomes a basis to determine / set DNEL or PNEC.
（http://guidance.echa.europa.eu/public-2/glossary.htm?lang=en#D_Dose descriptor)

12Topic-3
Derived Non-Effect Level (DNEL) and Predicted Non-Effect Concentration (PNEC)
in REACH(See CSA In-depth Guidance Document R.9 and R.10 for details)
In CSA in REACH, “Derived Non-Effect Level (DNEL)” and “Predicted Non-Effect Concentration(PNEC)” are used as dose descriptors for human health hazard assessment and for the environmental
hazard assessment, respectively.
The following are the methods commonly used for the above.
1) Available hazard data (including laboratory study, monitoring data, non-testing method) forthe corresponding tonnage level specified in REACH are collected and evaluated. Key
studies (generally, NOAEL, NOEC, etc.) are selected for the calculation of DNEL and PNEC.
2) Uncertainty Analysis: Assessment Factor (AF) is selected from administration routes, animal
species, difference of populations to be assessed (workers, consumers, aqueous organisms, soilorganisms, etc.), duration of administration, and other uncertainties.
Under REACH, all endpoints are considered for whether they can deliver a DNEL but normally therisk characterisation is only performed for the lowest DNEL or DMEL. The results of a laboratory
study are divided by an appropriate assessment factor, or several assessment factors get together
result in an overall assessment factor. When data which do not reflect the actual exposure situation(oral, dermal route or duration of exposure) are used for the assessment, it is decided that theuncertainty is high and therefore bigger value of the AF should be applied. For the risk
characterisation of long term or continuous exposure, AF for the results of a long-term study issmaller than that for the results of a short-term study.
DNEL and PNEC should be calculated by using an appropriate AF for each of the subjects to beassessed target population (workers, consumers, aqueous organisms, benthos, etc.), the route of
exposure (oral, inhalation, dermal), local or systemic effects.

3.3.3

When DNEL cannot be derived

It is generally considered that the risk cannot be excluded for a substance which induces effects by a modemechanism with no threshold, such as a genotoxic carcinogenic substance, even if the amount of exposure is
extremely low. For such a substance, an acceptable amount of exposure called Derived Minimal Effect Level(DMEL) can be used instead since DNEL cannot be obtained. DMEL is often calculated by using additional AF,
which is used upon extrapolation of effects from the dose associated with lifetime cancer risk, which is commonlyused in the risk assessment, or the high dose to the low dose. Special knowledge is required in the calculation of
DMEL, and an overview of the methodology is described in the CSA In-depth Guidance Document R-8 (seeTopic-4).

13

Topic-4
Quantitative/Qualitative approach in hazard assessment（See CSA In-depth Guidance Document R.8 for details）
REACH Annex I describes that derivation of DNELs for the human health and PNECs for theenvironmental hazard assessment shall be conducted in order to demonstrate that risks areadequately controlled by comparison of these DNELs and PNECs with exposure levels. Therefore,
conducting a quantitative assessment is considered as a standard approach of the chemicals safetyassessment in REACH.
However, the Annex I also specifies that “….it was not possible to determine a DNEL or a PNEC, aqualitative assessment of the likelihood that effects are avoided when implementing the exposure
scenario shall be carried out”.
In the CSA concise guidance document Part B.7.1.2.2, it is described that in case a DNEL for thehuman health is cannot be derived, a qualitative approach shall be applied. Examples that a DNEL
cannot be derived are described that; when test data are absent, non-threshold effect (e.g.
non-threshold carcinogens), and for an endpoint having a threshold level but the level cannot beestablished from test data （ e.g. irritation and sensitisation ） . For a non-threshold effect,semi-quantitative approach by deriving a DMEL (Derived Minimal Effect Level) is explained as oneof qualitative approaches. On the other hands, in CSA concise guidance document Part E.3 “Risk
Characterisation for Human Health” it is described that the quantitative or semi-quantitative
approach is carried out in advance by deriving a DNEL or DMEL. Furthermore, it is mentioned thatin case a DNEL or DMEL cannot be derived (e.g. corrosion/irritation, sensitisation, acute toxicity,
mutagenicity/carcinogenicity), a qualitative risk characterisation is conducted. For example,
appropriate RMMs should be taken according to the yes/no answer and severity from the tests
irritation/corrosion.
For the environmental hazard assessment, CSA concise guidance document part E.4.4 describes that,a qualitative risk characterisation should be conducted for remote marine areas or when either PEC
or PNEC cannot be properly derived. It means that when a proper PNEC cannot be derived, forexample, for those substances with a low water solubility and/or a high hydrophobicity (i.e. highbioaccumulative). For such substances an absence of short-term toxicity does not necessarily meanthat a substance has no long-term toxicity. Consequently, it is recommended to conduct a qualitativerisk assessment in order to decide if further long-term testing is required.

14

3.4

Environmental Hazard Assessment

3.4.1

Assessment of environmental hazard data

The environmental hazard assessment is implemented following two steps (See Topic-3)
・ Step-1:
Evaluation of the validity of all available data
・ Step-2:
Identification of the study or studies giving rise to the highest concern (key studies)
When it is considered valid for the assessment, the results of an in vitro study or a field study and a non-testing
method (QSAR, SAR, or read-across) can be used in addition to a laboratory study.
3.4.2

Calculation of Predicted No Effect Concentration (PNEC)

In the environmental hazard assessment in REACH, a PNEC needs to be calculated for each environmental
compartment (water, soil, etc.) which is assumed to be exposed. For the air compartment, normally only aqualitative assessment is possible. The PNEC for the aquatic compartment is preferably based on the No Observed
Effect Concentration (NOEC) in a long-term toxicity study. If no long-term toxicity studies are available, thePNEC can be based on the outcome of a short-term toxicity study (L(E)C50)8, but in that case the assessment
factor (AF) is higher (see the equation below). In many cases, only toxicity studies for the aquatic compartment
are available. In those cases, the PNEC of other target environments (sediment, soil) can be estimated using thestudy results of aquatic organisms, using the equilibrium partitioning method that is described in more detail in the
In-depth Guidance Documents R-10.
In order to estimate PNEC in the environmental hazard, the following formula can be used as well as the humanhealth hazard by applying various AF.

PNECcomp =Min (NOEC) or L(E)C50
AF

In the above formula, PNECcomp indicates the environmental compartment (water, soil, etc.) to be assessed, andMin (NOEC) or L(E)C50 indicates the minimum NOEC or L(E)C50 in the available study results.
See CAS In-depth Guidance Documents R-10 for the actual AF value and the method of calculation to estimate
the PNEC.

3.5

Physicochemical Hazard Assessment

3.5.1

Endpoints for physicochemical hazard assessment

Under REACH, the potential effects to human health shall be assessed for at least the following physicochemical
properties.
・ explosivity
・ flammability
・ oxidising potential
Above information can be obtained from laboratory tests and investigations but it may also comprise via
non-testing methods such as QSAR, SAR, read-across (See topic-5) (See CSA in-depth Guidance Document R.6).

8

L(E)C50: the test concentration at which 50% of the organisms is affected or at which 50% effect is measured for a specificallydefined endpoint (e.g. growth rate effects on algae).

15

Topic-5
Category Approach（See CSA In-depth Guidance Document R.6.2 for details）
Assessment of multiple chemical substances as a group, but not by the individual substance basis, isaccepted in REACH for the information required according to the tonnage level of the substance. Thismethod is called Category Approach. The category approach is a technical method to categorize
substances, which are assessed at the same time, into a group, and the read-across is a method to fulfil
the data gap (lack of required data) in the category approach. The chemical substances which aregrouped by the category approach must have similar physicochemical properties, health effects tohumans, and ecotoxicity or follow a consistent law determined by the structure of the chemical
substances.
Generally, as increased number of category members, the reliability of read-across to fill the data gap is
improved. When it is necessary to assess a large number of substances, the category approach is a very
useful method. In addition, from an animal welfare point of view, it can avoid unnecessary animal
testing.
Furthermore, when multiple substances are assessed simultaneously by the category approach, a toxicity
mechanism which has been shown with a specific substance can be used to verify its applicability to thesubstances of interest that have no data. Ideally, the substance of interest lies in between substances forwhich the required information is available and that show similar toxicity profiles.

16

3.6

Reliability Assessment of Study Data

In hazard assessment, reliability of available data is evaluated, and the most reliable data are used. If a study has
been conducted according to a method which is accepted internationally (OECD Test Guideline, etc.) and inaccordance with the GLP (Good Laboratory Practice) standards, the results of the study (mainly laboratory study)
are considered reliable (See Topic-6). The Klimisch Code is commonly used as an index for the reliability
assessment of hazard data in REACH.
If the study has not been conducted according to a method accepted internationally, or it does not meet the GLP
standards (or if such information is not available), the judgment of reliability is made on a case-by-case basis. It
may be possible to consider the study reliable if appropriateness of conditions or results of the study have beenverified in a document or if the identical data have been accepted in the database or assessment documents, etc.
The data obtained by a non-testing method (quantitative or qualitative structure activity relationship (QSAR,SAR), read-across from a similar substance, category assessment, etc.) can be accepted if reliability is adequately
verified. In such a case, however, transparency of the approach being used and the results, clarification of
application domain, and fulfilment of validation criteria must be assured (See CSA In-depth Guidance Document
R-6).

Topic-6
What is Klimisch Code: An Index for Reliability Assessment of Hazard Data?
(See CSA In-depth Guidance Document R.4 for details)
It is recommended in REACH to use a method called Klimisch Code to assess reliability of study
data. Generally, the data judged Score 1 or Score 2 is considered highly reliable, and an assessment isconducted using the data. If the data was judged Score 3 or Score 4, it is either not used directly forrisk assessment purposes or handled as reference data.
Score 1 = Reliable without restrictions: studies or data generated according to generally valid
and/or internationally accepted testing guidelines (preferably performed according to GLP) or inwhich the test parameters documented are based on a specific (national) testing guideline or in which
all parameters described are closely related/comparable to a guideline method.
Score 2 = Reliable with restrictions: studies or data (mostly not performed according to GLP), in
which the test parameters documented do not totally comply with the specific testing guideline, but
are sufficient to accept the data or in which investigations are described which cannot be subsumed
under a testing guideline, but which are nevertheless well documented and scientifically acceptable.”
Score 3 = Not reliable: studies or data in which there were interferences between the measuringsystem and the test substance or in which organisms/test systems were used which are not relevant inrelation to the exposure (e.g. unphysiological pathways of application) or which were carried out or
generated according to a method which is not acceptable, the documentation of which is not
sufficient for assessment and which is not convincing for an expert judgment.
Score 4 = Not assignable: studies or data which do not give sufficient experimental details andwhich are only listed in short abstracts or secondary literature (books, reviews, etc.).”Source： H. J. Klimisch, et. al., A Systematic Approach for Evaluating the Quality of Experimental
Toxicology and Ecotoxicological Data. Regulatory Toxicology and Pharmacology 25, 1-5 (1997)17

4. PBT Assessment
4.1 An Overview of PBT Assessment
Assessments of PBT/vPvB（Persistent, Bioaccumulative and Toxic / very Persistent and very Bioaccumulative(Substances)） is required for all substances which are manufactured and imported at quantities equal or morethan 10 tons per year and are not exempted from REACH registration. Overviews of the criteria for PBT/vPvB
assessment, the assessment methods including the screening evaluation and the instructions in CSA GuidanceDocuments regarding the required measures for substances judged as PBT/vPvB are described in this chapter.

4.2 Aim and Procedures of PBT Assessment
PBT/vPvB assessment is carried out following steps and objectives.
Step-0:A screening assessment of PBT/vPvB substance, which is shown in Table 4-1. According to
the results of the screening, PBT/vPvB assessment can be discontinued if the substance does
not meet PBT/vPvB.

Step-1:

Whether the substance fulfils the criteria given in Annex XIII (See Table 4-2).
If it is concluded that the substance is not a PBT/vPvB substance, the PBT/vPvB assessment
stops after comparison with the criteria. An exposure and risk assessment as for a non-PBT/
vPvB substance could however be required if the substance is dangerous in accordance withthe classification criteria of Council Directive 67/548/EEC. Therefore PBT assessment isconducted independent of the normal hazard assessment.

Step-2:

If a substance is confirmed to be a PBT/vPvB substance, the registrant needs in a second stepto estimate the amounts of the substance related to the different environmental compartments
during all activities carried out by the registrant and all identified uses (IUs). In addition, it isnecessary to identify the likely routes by which humans and the environment are exposed tothe substance, subsequently needs to estimate the all possible exposure routes, amount of
exposure and duration through the life cycle of the substance.

Step-3:

The registrant shall use the information obtained during the emission characterisation step, for
implementing on his site, and recommending to downstream users for their operational
conditions (OCs), risk management measures (RMM) which minimise emissions andsubsequent exposures of human and the environment throughout the lifecycle of the substancethat results from manufacture or identified uses.

4.3 Screening Assessment of PBT SubstanceIn the assessment of PBT/vPvB substance, persistency, bioaccumulative, and toxicity are evaluated in thescreening assessment, and eventually, it can be judged if it corresponds to PBT/vPvB substance. The judgment
criteria for the screening are shown in Table 4-1.
Generally, the substance is not considered persistent in PBT criteria if it is readily degraded in one of the Ready
Biodegradability studies as described in the OECD301 guideline or inherently biodegraded in the OECD302A,
OECD302B or OECD302C inherent biodegradability study. .Similarly, bioaccumulation potential is considered
low if log Pow is 4.5 or less in the “OECD TG107 Octanol- Water Partition Coefficient Study.”
For toxicity to the environmental organisms, a substance is considered as PBT substance (for environmentalorganisms) if L(E)C50 is 0.01 mg/L or less in an acute toxicity study of algae, crustacean and fish, regardless ofthe presence or absence of long-term study data. In a case where it is not clear if the substance meets the
PBT/vPvB substance criteria in the screening assessment, a step-by-step approach, which is described in section
4.2 in this document, is used in order to make a final assessment of persistency, bioaccumulative, and toxicity
criteria.
18

Table4-1: Screening criteria for PBT Assessment
Property

Persistence

Bioaccumulation

ToxicityType of data
Ready biodegradability study（OECD TG301 etc）
Specified tests on inherent
biodegradability（OECD 302B、C, etc）
Convincing evidence that asubstance can biomagnify inthe food chain (e.g. field
data）
Octanol-waterpartitioncoefficient (OECD TG 107
or estimated by reliable
QSAR）
Short-term aquatic toxicity（e.g. OECD TG201、202、
203）
Avian toxicity (subchronicor chronic toxicity or toxic
for reproduction)（e.g. OECD TG 205、206）

Criteria
Readily biodegradable

Screening assignment
Not P and not vP

Inherently biodegradability> 70% mineralization within 7d (DOC
removal), and within 14d (O2 uptake); no
pre-adapted inoculum

Not P

e.g. BMF > 1

B or vB, definitive
assignment possible

Log Kow < 4.5

Not B and not vB

EC50 or LC50 < 0.01 mg/L

T criterion consideredtobedefinitely
fulfilled

NOEC < 30mg/kg （feed）

T

4.4 PBT and vPvB Criteria
The PBT/vPvB criteria in REACH are shown in Table 4-2. In terms of vPvB substance criteria, a substance whichmeets the persistency and potential of accumulation criteria, is subjected regardless of hazard.
Table 4-2: PBT and vPvB criteria according to Annex XIII of the REACH
Property

Persistence

Bioaccumulation

Toxicity9

PBT Criteria
T1/2 > 60 days in marine water, orT1/2 > 40 days in fresh-estuarine water or
T1/2 > 180 days in marine sediment orT1/2 > 120 days in soil

vPvB Criteria
T1/2 > 60 days in marine , fresh or
estuarine water, orT1/2 > 180 days in marine, fresh or
estuarine sediment orT1/2 > 180 days soil

BCF > 2000 L/kg
NOEC < 0.01 mg/L for marine or freshwaterorganisms, orSubstance is classified as carcinogenic (category 1 or2), mutagenic (category 1 or 2), or toxic toreproduction (category 1, 2 or 3), or
There is other evidence of chronic toxicity, as
identified by the classifications: T, R48, or Xn, R48
according to Directive 67/548/EEC.9

BCF > 5000 L/kg-

Council Directive 67/548/EEC for the classification of dangerous substance can be found at following web site.
http://ecb.jrc.ec.europa.eu/classification-labelling/19

4.5 Further Measures to be Taken When the Substance is Confirmed to be PBT or vPvB
If it is concluded that the substance is a PBT or vPvB substance, or that it should be treated as such, the registrant
must conduct an emission characterisation and a risk characterisation for PBT/vPvB substances in accordancewith Article 14 (4).
Generally, if a substance contains one or more constituents with PBT/vPvB properties in individual amounts >0.1% (w/w) or if transformation/degradation products with the respective properties in amounts > 0.1% are being
generated, the substance must be subjected to PBT/vPvB specific emission characterisation and risk
characterisation. However, for the sake of relevance of risk exerted by the amount of a PBT/vPvB substancemanufactured/imported by a registrant, and hence with regard to the requirements for risk characterisation andnature of RMM to be implemented, it may be considered to use a threshold value of 10% (w/w) for the total of all
constituents or transformation/degradation products having PBT or vPvB properties, if it is possible to estimate
with sufficient certainty that the total manufacture/import or supply of PBT/vPvB constituents in that substanceand the total amount of degradation/transformation products with PBT/vPvB properties generated by that
substance do not exceed 1 t/y10.
The main objective of the emission characterization is to estimate the amounts of the substance released to thedifferent environmental compartments and to identify the likely routes by which humans and the environment are
exposed to the substance. A registrant has only to take care of his own tonnage. In co-operation with his
downstream users he has to cover, where relevant, any manufacture in the EU he is responsible for, his own uses
and all identified uses including all resulting lifecycle stages.
The principle tool to achieve this objective is exposure scenarios (ESs). CSA Concise Guidance Document Part D
and in-depth Guidance Document R.12 to R.18 provide guidance on how to develop ESs for substances in general.
As PBTs and vPvB are substances of very high concern, the registrant shall pay special attention to the level ofdetail of his assessment and whether its accuracy and reliability is sufficient for a PBT/vPvB substance. Where
generic scenarios and assumptions may be sufficient for exposure assessment of non PBT/vPvB substance,
specific scenarios and data will most likely be needed throughout an emission characterisation for PBT/vPvB
substances.
The objective of a risk characterisation for substances satisfied the PBT/vPvB criteria is to use the information
obtained in the emission characterization step to implement on a registrant’s site or to recommend his
downstream users RMMs which minimise exposures and emissions to humans and the environment throughout
the lifecycle of the substance that results from manufacture or identified uses (Annex I (6.5). To this end,
minimisation of exposures and emissions to humans and the environment needs to be considered throughout thedevelopment of ESs. In this way, the appropriateness and effectiveness of RMMs and OCs should be assessed in
the development of the ES.

10

Please note that the proposed one ton per year threshold for the total of compounds with PBT/vPvB properties in a substanceconsisting of more than one component (be it a preparation or a multi-constituent substance) is not an ‘allowable release’ threshold. It
refers instead to the content in a substance that will need to have appropriate risk assessment and management justified in thechemical safety report. 1 t/y is the level at which the registration requirement under REACH normally begins to apply if a substance
was supplied alone or in a preparation. 1 t/y is also the trigger for registration in an article. Therefore, this amount is considered to bea suitable threshold level for relevance and hence adaptation of required risk assessment efforts and, depending on the results of risk
assessment, possibly risk management measures.

20

5 Exposure Assessment
5.1 An Overview of Exposure Assessment in REACH
The methods to develop Exposure Scenario (ES) and to conduct an exposure assessment, including estimation of
the level of exposure, in CSA Guidance Document are illustrated in this document. Although the focus here isplaced on how to develop ES, an overview regarding estimation of the level of exposure is also provided.
An ES is a set of information describing the conditions in which the risk associated with the identified use (IU) of
a substance can be controlled. This includes Operational Conditions (OC) (e.g., the duration and frequency of useor the amount of used, the process temperature or the pH) and necessary RMM (Risk Management Measures)(e.g., local exhaust ventilation or some sort of gloves, waste water and gas treatment). If a manufacturer orimporter fails to describe relevant and realistic measures that control risks for a substance in a certain use he can
not cover this use in his exposure scenario. Otherwise he has to explicitly advice against that use in the safety data
sheet. Exposure scenario building is likely to include dialogues (i) between manufacturer and downstream users(DUs and (ii) from downstream user to downstream users further down the supply chain.
The route of exposure to humans via the environment is shown in Figure 5-1 as examples of exposure routes.

Figure 5-1 Human exposure routes via the environment21

5.2 Actors in supply chain under REACH
Under REACH each actor of the supply chain is defined as follows (Article 3)
・

Actors in the supply chain: means all manufacturers and/or importers and/or downstream users in a supply
chain:・ Manufacturer: means any natural or legal person established within the Community who manufactures a
substance within the Community.
・ Importers: means any natural or legal person established within the Community who is responsible forimport.
・ Downstream user: means any natural or legal person established within the Community, other than the
manufacturer or importer, who uses a substance, either on its own or in a preparation, in the course of his
industrial or professional activities. A distributor or a consumer is not a downstream user.
・ Distributor: means any natural or legal person established within the Community, including a retailer, who
only stores and places on the market a substance, on its own or in a preparation, for third parties.

5.3 Determinants for Exposure Scenario Development
Parameters associated with several characteristics (the characteristics of the substance, processing / product, or
surrounding environment), which are required to determine the substance release and exposure to the workers,
consumers, and environment must be included in the Exposure Scenario (ES). These are called “the main
parameters determining the release and exposure: determinants)” (See Table 5.1). These determinants are includedin the ES as items which are further specified based on the Operational Conditions (OC) and the existing Risk
Management Measures (RMM). For instance, processing / product features are subdivided into items such as theduration of the product use (durable years), the amount to be used, and RMM, and these are further subdivided
into comprehensive parameters which determine the substance release and exposure.
The manufacturer and/or importer should develop the initial ES from the OC at the time of manufacturing, theexisting RMM, the identified use (IU) as well as from appropriate and available information in the life cycles. In
the initial ES, a scenario which can be assumed in the substance life cycle is established. It is also necessary at thisstage to specify the determinants associated with biological exposure factors (dermal, oral, inhalation routes andenvironmental toxicity) and hazard information in accordance with ES.
The level of exposure is estimated in the ES, and a risk characterisation is performed. According to the results,
RMM or several characteristics may be reviewed based on “the main parameters determining the release andexposure (the main parameters).” The integrated ES, which was established as above, is documented in a standard
format, and recorded in the CSR and the SDS and communicated to downstream users (DUs) as information.

22

Table 5-1 Examples of determinants of exposure
Determinants of
exposure
Molecular properties
Physico-chemical
properties of substanceStability

Lifecycle stage ofsubstance or product towhich the ES refers
Type of activity orprocess

Time pattern of use
Technical conditions ofuse
Characteristics ofchemical productUse quantity

Risk Management
Measures (RMMs)

Surrounding absorbing
or diluting release
Biological exposure
factors

Examples (not exhaustive)

Remarks

Substance characteristics
Molecular weight
Gives an indication of bioavilability
Molecular size
Vapour pressure
Exposure determinant at workplace andOctanol-water partition coefficientin the environment
Water solubility
Biological degradation, hydrolysis
Exposure determinant related to
Photodegradation, atmospheric degradation
degradation in environmental(half-life in water, soil, air)compartments incl. sewage treatment
Characteristics of processes and products
Manufacture of substance, formulation, final useof chemical products, service life of substances
Identify relevant exposures for all target
in articles, waste phase.
groups, supports selection of suitable
For example: synthesising substances; mixing
broad ES; supports the selection ofsubstances; using substances as process aids;
pre-set process or product categories inusing chemicals by spraying or by dipping or bytier 1 tools for exposure assessment.
brushing; using substances in articles e.g.
wearing textiles, spending time in house;
Determinant related to pattern of
Duration of activity/use
exposure (short term vs. long term) and
Frequency of activity/use
corresponding choice of PNEC orDNEL
Level of contaminant of process
Determinant related to exposure of
Temperature, pH, etc
humans and environment
Determinant related to exposure of
Weight fraction of substancehumans and environment for
Fugacity, dustiness, volatility of productpreparations or products
Determinants for the exposure potential
Kg [t] per time or activity
per time or per activity
Local exhaust ventilation (workplace)
Personal Protective Equipment (workplace)
RMMs as integrated element of theOn-site waste (water) treatment e.g. oil-watertechnical product or process, or as
separation
additive measure; determinant of theextent to which exposure can be
Municipal sewage treatment, waste treatment
mitigated or prevented;
Package design preventing dermal or inhalation
exposure (product safety)
Characteristics of surrounding
Exposure determinant based on the
Room size and ventilation rate; river water flow;
assumption that even distribution of
capacity of sewage system
substance takes place
Determinant of the dose to which a
Inhalation volume, body weight
human is exposed and corresponding
choice of PNEC or DNEL

Some of the determinants listed in Table 5-1 are usually not iterated by the registrant but are set realistic (default)
values, namely substance characteristics and surrounding characteristics. Other parameters can and have to be
determined in the ES during the iterative process by the registrant. REACH distinguishes two types of thesechangeable determinants to be reflected in the exposure scenario: the operational conditions (OCs) and risk
management measures (RMMs).

23

5.4 Development of Exposure Scenario
Exposure scenarios shall be developed for;i) The manufacturing process andii) For identified use including own uses by the M/I, and uses further down the chemical supply chain
and consumer uses,iii) Life cycle stages resulting from manufacture and identified uses (article service lie and waste life
stages).
M/I will start his assessment with all available relevant information on the operational conditions and the existingrisk management measures in manufacture, identified uses and resulting life cycle stages (initial exposure
scenario). Downstream users or their organisation may have already compiled such information in a generic ES
format so that M/I can directly proceed with completing the initial ES and estimating exposure for the uses
covered. He will then estimate exposure corresponding to the available information. Often in a first iteration,
standard tools for exposure estimates that are sufficiently conservative will be applied (Initial step: Tier 1).
If measured data on exposure levels are available, reliable, and representative for the operational conditions andrisk management measures described in the initial exposure scenario, these data can be used for the exposure
estimate. The same applies for cases where there is enough information to use higher tier (Tier 2 assessment)
exposure models for the first estimate.
M/I will collect further details on release and exposure determinants when it is not possible to demonstrate controlof risk based on the initial ES. In some cases hazard data are also refined as well, but that is not further describedhere.
The process of developing the ES may vary case by case depending on the available information, but in particularwhen relatively little information is available upfront, the general process will follow the 14 steps presented in
Figure 5-2 and Table 5-2. The standard workflow is based on categorising processes and products in which thesubstance is used. The choice for specific categories leads to a selection of preset generic exposure scenarios
which can be connected to existing tier 1 exposure estimation tools. If M/I has sufficient information available tobuild exposure scenarios and document the corresponding exposure estimates based on measured data or higher
tier models he can shortcut the process. In such situations he can directly go to step 6 described in Figure 5-2 andTable 5-2 (invite DUs for feedback) or step 10 (run CSA based on measured data or higher tier models),
depending on the state of dialogue with the downstream users (See CSA Concise Guidance Document Part D.2,
D.3).
The general workflow for the building an exposure scenario is shown in Table 5-2 and Figure 5-2.

24

Table 5-2: Workflow of building exposure scenarios
Workflow
1

2

3

4

5

6

7

8

9
10
11

12

13

14

Map use of substanceAnalyse the market of the substance based on existing in-house information.
Invite DUs to provide information on is needed
Compile all available information on OCs and RMMs and related release/exposure levels during thelife cycle of the substanceStart with existing in-house information. Invite DUs to provide information if needed.
Select appropriate process or product categories related to the uses identified.
Define the information needs based on ES standard format and the selection of the tool (exposure estimation
models). Take into account the domain of the tool with regard to the hazard profile and the physical state of
the substance to be assessed.
Build initial exposure scenarios based on the input data needed for Tier 1 exposure estimate
Check further available information on OCs and RMMs from• DUs and/or their organisations (including initial exposure scenarios)• Product or branch specific RMM packages in the RMM library.
Make an initial exposure estimation and initial risk characterisation by obtaining relevant exposure data for
the ES.
Complete initial ES
Where control of risk can be demonstrated on the basis of initial risk characterisation, complete the initial ES
by further describing the corresponding operational conditions and risk management measures.
Invite and receive feedback from representative customers or DUs organisations• Relevant uses are (not) covered• RMMs or OCs are appropriate or not• The descriptions in the ES are understandable to the addressees
Identify and use additional information (if needed), based on feedback;• Refine RMM and OC in the initial ES before and/or• Refine information on substance properties (e.g. DNEL for a certain route needed)
Carry out further CSA runs (exposure estimates, risk characterisation and uncertainty analysis)
Decide on further iteration needed, and/or control of risk can be demonstrated, and/or further testing isneeded.
If initial model (Tier 1) cannot demonstrate the control of risk, decide whether measured data or higher
tier model is needed.
If control of risk can be demonstrated based on tier 1, progress to step 11.
Apply another model or use measured data to
Refine the ES and demonstrate control of risk.
Conclude the exposure estimation and risk characterisation (including uncertainty analysis)
Derive the integrated exposure scenario by linking all OCs and RMMs within the exposure scenarios.
• Document the operational conditions and risk management measures required for human health andenvironment and corresponding exposure routes for each use covered by the ES.
• Consider impacts of OC/RMM across exposure routes. Select the OC/RMM leading to control of risk
related to all routes of exposure.
Merge ES if appropriate
Carry out cross-comparison on the final exposure scenarios and conclude which scenarios to merge based on
similarities in risk management and operational conditions.
Document the deliverables of the exposure assessment
Document the results of exposure assessment in the CSR and SDS.

25

Invited or
pro-active
info packfrom DUs

1. Map use of substance (in-house information)
2. Compile available information on condition of use

3. Select appropriate process and product categories

Start up information
Map of uses
Inventory of
information on OC
and RMM

4. Build initial ES and run first exposure estimation
5. Complete initial ES (short title, covered activity,
OC, RMM)
6. Invite and receive feedback from representative
DUs

8. Carry out further CSA runs (iteration) with theselected tool

Information available
for higher tierassessment

9. Decide whether measured data or higher tier model
needed.
10. Apply other models or measured data if needed,
run CSA
11. Conclude
characterisation

exposure

estimation

and

risk

12. Derive integrated ES by linking all OCs andRMMs

Final Output
・Final ES（no further
testing）
・final ESs (testing
proposed)・uses advised against

13. Merge different ES into a broader ES (optional)• CSR, ES for SDS

•
•
•
•

Hazard classification and PBT/vPvB
Dose/concentration – response characterisation
Chemical-physical properties (driving release and exposure）
Need for exposure information related to waving or testing

7. Identify additional information (if needed)

14. Document in CSR, SDS

Figure 5-2 Steps for ES development（each number corresponds to one in Table 5-2）

The process of developing the ES may vary case by case depending on the available information, usually
implemented steps described in Figure 5-2 and Table 5-2. Standard workflow is based on the descriptors(categories) presented in chapter 5.5 and products in which the substance is used. Selection of a specific category
is used for the selection of generic ES which is shown in section 5.13 of this document that the initial exposure
estimation tool (tier 1). Where sufficient information for the development of the ES is available, these steps can beshortcut.

26

5.5 Descriptors for Establishment of Exposure Scenario
Five types of descriptors are used in REACH with regard to the use of a chemical substance in order to develop
the Exposure Scenario (ES) and to estimate the level of exposure. These are 1) Sector of Use (SU), 2) Chemical
Product Category (PC), 3) Process Category (PROC), and 4) Article Category (AC). See CSA In-depth GuidanceDocument R.12 for details of each descriptor. In addition, Environmental Release Category (ERC) is used toassess the environmental exposure (see CSA In-depth Guidance Document R.16).
The first four descriptors are illustrated in Figure 5-3. These descriptors are the important decision criteria for the
preparation of initial ES or in the use of the estimation model for the amount of exposure at the tier 1 stage.

Substance A

Substance…

Where is it used?

Brief generaldescription ofuse

Sector of UseUse Descriptor
SystemProduct Category

Manufacturingindustry

Public domain

Coating, paints

How is it used?
Short title forESspraying

Process Category

brushing

Processed into
article?

Construction
articlesArticle Category

Figure 5-3 Descriptors for the development of ES

5.6 RMM: Risk Management Measures
In order to control the risk appropriately, RMM are used in REACH as measures to reduce exposure. The effect of
RMM can be defined quantitatively as the reduction rate for the concentration of exposure and the amount ofemission (release). However, the result of measurement of the actual exposure concentration may be a better index.
In reality, the effect of RMM changes with various factors, and it is not possible to determine appropriately by asingle value.
The effect of RMM can be obtained using a certain appropriate default value, which is used in the estimation
model for the amount of exposure. The 31 RMM and the safety guideline listed in Table 5-3 are recommended in
REACH and are included in the RMM library. The RMM library corresponds to measures such as a protective
equipment to reduce exposure in various situations, product manufacturing / processing and to the workers within
Europe. It is not recommended to refer to the contents of RMM library in the CSR since the efficacy evaluation
has not been completed yet in the CSA Guidance Document. Although the RMM library can provide information
regarding the effect of RMM, efficacy should be assessed individually by the actual downstream users (DUs), andRMM library should be utilized as the information source for this.

27

Table 5-3: RMMs in tentative RMM library and summary of safety guidelines11
Product-substance Related:
1. Limiting concentration of hazardous or non-hazardous
ingredient2. Change of physical state (e.g. powder -> pellet)
3. User friendly packaging (reducing handling)
4. Info /Guidance /Manual other than label and Safety Data Sheet
Marketing and use related
5. Marketing and Use – General
6. Product safety/ advice
Process/ Control Changes:
7. Process Control/ Change
8. Automation
9. Containment of process equipment
10. Cleaning of process equipment
11. Spill Containment Measures
12. Reduction and cleaning of air emissions
13. Reduction and cleaning of waste water
14. Reduction of waste, disposal of waste
Ventilation Control:
15. Local Exhaust Ventilation – (partial) enclosure
16. Laminar Flow Booths & Laminar Flow Benches
17. Local Exhaust Ventilation – captor hoods

18. Local Exhaust Ventilation – receptor
hoods
19. applications
General Dilution Ventilation:
20. Dilution Ventilation
Organisational:
21. Management Systems
22. Operating Practice
23. Competence and training
24. Supervision
25. Monitoring
26. Health Surveillance
Good Hygiene Practice & Housekeeping:
27. Good Hygiene Practice & House keeping
Personal Protective Equipment
28. Body protection
29. Hand protection
30. Respiratory protection
31. Face/ Eye protection

5.7 Outline of the Exposure Estimation Method
When an initial exposure scenario has been developed it has to be assessed whether the information collected issufficient to demonstrate that the risks occurring from the manufacture and all identified use(s) are controlled.
Often the collection of information and the risk characterisation will be an iterative process until it can be
confirmed that the risk is controlled. The risk characterisation requires the comparison of exposure estimates andderived no-effect or minimum effect levels (DN(M)EL, PNEC). This can be done by generating exposure
estimates for all identified uses described in the exposure scenario.
The process for estimating exposures during the development of ES is usually conducted in two steps:
The first step (also termed Tier 1) aims at estimating the “reasonable worst-case” exposure for the conditions ofuse described in the initial ES. Such estimate can be obtained using actual measurements or standard exposure
models and selecting from preset conditions of use as defined for Process Category (PROC) or Chemical ProductCategory (PC).
A subsequent step (Tier 2) is required if control of risk cannot be demonstrated for the initial ES in the first step
(Tier 1).
Tier 2 focuses on typical well-defined exposures with appropriate knowledge on the confidence limits involved,
based on uncertainty and variability of the relevant parameters. The estimation model for the amount of exposure
used in Tier 2 generally requires more detailed input on conditions for processing or use, physiochemical
properties, and RMM, etc. compared to that in Tier 1. Although a certain level of expert knowledge is required in
the Tier 2 model, it can derive a result which seems closer to the actual exposure compared to the Tier 1 model.

11

At present, the library is in an early stage of development. An outline of the library can be obtained at CEFIC’s web site below.

http://www.cefic.org/Templates/shwStory.asp?NID=494&HID=645&PHID=643

28

5.8 Use of Measured Data
Ideally, the process for estimating exposure would be based on actual measurements for the use of the substance ineach scenario. However, this will not always be possible. Therefore, it will often be necessary to either combine
actual and modelled estimates of exposure, or to rely solely on modelled estimates. Sometimes it may also be
possible to estimate exposure based on the measured data of another substance which however processes similar
properties regarding its environmental fate.
However, the use of measured data needs special attention i.e.
・・・・Are the data appropriate for the scenario being investigated, i.e. is there sufficient information on RMM andOC that were in place when measurements were performed?
Are the data supported by sufficient contextual information such that their relevance to the scenario can be
determined?
Have the data been obtained using appropriate sampling and analytical techniques to yield the necessary
sensitivity?
Are sufficient data points available to be seen to be representative of the exposure scenario being evaluated?

For measured data related to environmental concentrations a number of additional considerations have to be
made:
•
•

Have the data been properly assigned to the appropriate spatial scale (local or regional scale) by taking into
account sources of exposure and the environmental fate of the substance?
Have background concentrations been taken into account for naturally occurring substances?

Provided such data are of a suitable quality and are supported with sufficient information that enables them to be
seen as being representative of an Exposure Scenario, then such data will reflect the reality of the use rather than
any modelled representation (see CSA in-depth Guidance Document R.14 – R.18).

5.9 Occupational Exposure Estimation Assessment
In the workplace, exposure to chemicals may occur via three exposure routes: inhalation, dermal contact and oral
intake. However, when proper hygienic measures are taken the direct oral intake is generally considered to be
negligible and is not assessed for workers. For the determination of exposure through the other routes, one can use
either measured data and/or predictive estimation models. Where measured data are available, then these are
preferred to exposure estimates derived from models. Furthermore, while measured data might often be available
for inhalation exposure, data that characterises dermal exposure is much less frequent. It will therefore benecessary to develop any estimate of exposure for the Scenario based upon combinations of available data (realand modelled estimates) (see CSA in-depth Guidance Document R.14).

5.10 Consumer Exposure Estimation
Consumer exposure estimation will need to consider 3 exposure routes (i.e. dermal, oral, inhalation). Each
exposure route needs to be calculated separately. An exposure scenario can be derived using a tiered approach to
exposure estimation. Initially a 1st tier exposure estimate can be used to derive a “reasonable worst case” scenario.
Subsequent higher tired (tier 2) estimates can be used to further characterise the exposure (see CSA in-depth
Guidance Document R.15).
Inhalation: In a Tier 1 assessment, it is assumed that all substance is released as a gas, vapour or airborne
particulate into a standard room. This may be due to direct release or by evaporation from a liquid or a solid
matrix. At subsequent iterations or in higher tier assessments, other parameters are considered such asconcentration of substance in the air, the number of rooms, ventilation rate of the room or rooms and the rate at
which a substance is released into the room or rooms.

29Dermal, two options:
A: The substance is contained in a preparation. This option is e.g., applicable when hands are put into a solution
containing the substance under evaluation.
B: Substance migrating from an article; applicable for example when residual dyes in clothing are in contact withskin and migrate from the clothing.
Oral, two options:
A: Substance in a product unintentionally swallowed during normal use.
B: Substance migrating from an article; applicable for example when a substance migrates from a pen or textile
that is mouthed.

5.11

Environmental Exposure Assessment

For the environmental exposure assessment, consideration should be made for;
•
•
•
•
•
•
•

Fresh surface water (including sediment)
Marine surface water (including sediment)
Terrestrial ecosystem
Top predators via the food chain (secondary poisoning)
Micro-organisms in sewage treatment systems
Atmosphere – mainly considered for chemical with a potential for ozone depletion, global warming, ozone
formation in the troposphere, acidification
Man indirect, i.e. man exposed via the environment

Based on the identified use by the ES, estimation of the level of exposure should be done for all possible target
routes separately (see CSA in-depth Guidance Document R.16).

5.12

Use of the Final ES in the Supply Chain

The final exposure scenario(s) for a substance must be communicated down the supply chain. The format and thephrasing of the exposure scenario should meet three requirements:
1. The RMM advice should be practically useful for the recipient of the exposure scenario:•
The recipient may be a formulating downstream user for whom the ES is a source of three types of
information:• Practical advice relating to the formulator’s own technical activity (mixing substances and/or
preparations)• Information relevant to the formulator’s choices on product composition and design.
• Information and advice relevant to the formulator’s customers and further downstream users•
The recipient may be an end-user for whom the ES is a source of i) practical advice relating to its
own technical activity and ii) information relevant with regard to control of risk further down the
supply chain (articles and waste).
2. The assumptions under which the supplier regards the uses of his customer and the uses further down the chain
as safe must be transparent to the downstream user
3. The ES should include brief advice on how the recipient of the ES can check whether the conditions in the ES
are met in practice at the user’s level.

30

5.13

Features of Exposure Estimation Models

Following exposure estimation models are recommended to use under REACH. Outlines of each model are shown
below.
ECETOC TRA occupational
https://www.ecetoc-tra.org/index.asp
Occupational exposure
・ Clear structure
・ A parameter related to process category is used as basis for assessment
・ Duration of process/activity is taken into accountStrengths
・ Scenarios (process categories) based on EASE and expert input from industry stakeholders
・ The calculated effectiveness of local exhaust ventilation depends on process and is thus not
set at a constant value. This is in accordance with observations. However, the tool is currently
not able to distinguish between different types and efficiencies of LEVs.
・ Some process categories appear to overlap; the choice is not always clear
・ The number of process categories appears to be insufficient to cover every first Tierassessment
・ Processes categories are described in expert language; non experts in the field of worker
exposure (assessment) therefore find the tool difficult to use
・ Except through differentiation of processes/activities/operation units and in duration ofactivity, influence of amount of product used on exposure level cannot be taken into account
Limitations
・ Only “local exhaust ventilation” and (indirectly) changes in processes/activities/operation
units and duration can be chosen as “risk management measures”
・ Web-based version and paper version (ECETOC Technical Report No. 93) do currently not
fully agree; the paper tool is at the moment the preferred choice. The foreseen update of thetool will include streamlining in this respect.
・ Compared to measured data (RISKOFDERM project) the dermal exposure for situations withlocal exhaust ventilation is underestimated.
・ Using the most conservative estimate of both process categories if the choice is not clear
・ Assume that small amounts are related to short durations of use
Compensation ・ Consistently use the paper version as basis for the estimations (the report can be downloaded
for limitations
from the internet)
・ Assume no local exhaust ventilation for dermal exposure estimates (to reach a conservative
estimate)
URL
TargetCOSHH-BAuA-Tool
http://www.REACH-helpdesk.de/en/Exposure/Exposure.html
Occupational exposure
・ Very clear and user friendly structure
・ The output has been shown basically sound for a number of ES
Strengths
・ Provides control strategies for a range of common tasks, e.g. mixing, filling, etc.
・ Control guidance sheets are available on the Internet
・ The estimates are generic in nature and therefore uncertain to some extent.
・ It is not possible to use the assessed exposure ranges as a basis for further iterations, e.g.
considering the duration of exposure (only the influence of short term exposure, i.e. < 15
min/day, is considered)
Limitations
・ Validation of the concept is, as always for exposure estimation models, limited
・ Not suited for gases (handled or released)
・ Should not be used for tasks where fumes are generated or where dusts are formed throughabrasive techniques・ Not suited for CMR substances.
・ The substance concentration (in products) is assumed to be 100%.
Compensation ・ The duration of exposure is assumed to be the shift length. If the activity is carried out for lessfor limitations
than 15 minutes a day the next lower range of predicted exposure can be assumed andcompared with the DNEL.
URL
Target31

ConsExpo
URL
http://www.rivm.nl/en/healthanddisease/productsafety/ConsExpo.jsp
TargetConsumer exposure
・ Builds on the EU-TGD for existing and new substances (2004), which is accepted within theEU.
・ Contains a database with default values for a range of products and uses (although input data
Strengths
mostly relate to higher tier models, not Tier 1)・ Documentation for default values is available in so called ‘fact sheets’.
・ Free of charge.
・ ConsExpo currently has no explicit facility to work with a diversity of consumer productcategories at Tier 1. If default pre-set values for product categories are being developed in
Limitations
near future, a link between these categories or incorporation of these categories in the
database of ConsExpo is needed.
・ Risk management measures are not mentioned explicitly.
Compensation ・ Product-related RMMs can be accommodated in ConsExpo by changing the input parameters
for limitations
to the Tier 1 equations (see Section D.4.5).

EUSES Consumer
http://ecb.jrc.ec.europa.eu/euses/
Consumer exposure
・ Builds on the current EU-TGD, which is accepted within the whole EU
Strengths
・ Requires few data
・ Free of charge
・ EUSES currently has no explicit facility to work with consumer product categories
subdivided in preparation categories and article categories. Initial product category settings
Limitations
need to be transferred to the input of EUSES.
・ As in any other available consumer exposure tool, risk management measures are notmentioned explicitly.
Compensation The inclusion of RMM for the consumer can be handled manually in the tools.
for limitations
URL
Target32

EUSES/ERCs
URL
Targethttp://ecb.jrc.ec.europa.eu/euses/
Environmental exposure
・ Builds on the current EU-TGD, which is accepted within the whole EU・ Requires few data for a first assessment
・ Refined data on operational conditions and RMM can be directly inserted into the calculation
Strengthsof emissions at Tier 1 level during the CSA process. The same applies for refined substancecharacteristics that can be entered into the tool
・ Available free of charge from http://ecb.jrc.it/euses/
・ For the default emission factors in the current EUSES is it not clear which operational
conditions and which risk management measures are assumed to be already in place. Thus
iteration may lead for example to a duplication of RMMs already included in the default
emission factor.
Limitations
・ The correlations used for the derivation of substance parameters, i.e. mainly partition data, arenot valid for inorganics and surfactants. Whenever measured partition and degradation data
are available, these should be used in the calculations. This is of very high importance formetals, inorganic compounds and surfactants.
・ These limitations are the reasons for introducing the ERCs. The ERCs can be loaded in
EUSES from input files.
・ To introduce the effect of RMMs and changes in the conditions of use, the presets for the
ERCs can be replaced with own estimates, information from downstream users or measured
data.
・
When dealing with metals, inorganic compounds and surfactants, use - if available - measured
Compensation
partition data. For cationic (positively charged) compounds, you may use very high partition
for limitations
coefficients (soil-water, sediment-water, sludge-water). For anionic (negatively charged)
compounds you may use very low partition coefficients (soil-water, sediment-water,sludge-water). If no measured partition data are available, you may run a set of simulations:
one where you use very high partition coefficients (soil-water, sediment-water, sludge-water)and one with very low partition coefficients. You can then use the results giving the highest
predicted risk quotients.

URL
TargetStrengths

Limitations

Remark

EUSES Spreadsheet
RIVM（www.rivm.nl） and CEFIC（www.cefic.org）
Environmental exposure
・ Similar advantages as EUSES for environment and indirect exposure of man
・ For the experienced user having specific release data at his disposal, the emission estimation
module in the spread sheet version provides more transparency of the calculations.
・ Allows integration in dedicated exposure calculation tools.
・ Available free of charge
・ Not linked to any process or product categories, thus, release data are to be entered manuallyby user and the effect of RMMs needs to be introduced by reduced emission factors.
Spreadsheet software needs to be protected for algorithm stability since it is vulnerable tointroducing mistakes. As a default, the sheets in the TGD Excel are write-protected, except thecells for specifying the variable input parameters. Great care should be taken if disabling thiswrite-protection.

33

6 Risk Characterisation
6.1 An Overview of Risk Characterisation
In REACH, it is required to demonstrate in CSA that the risk of the registered substance to humans orenvironmental organisms under the condition of identified use (IU) is at the acceptable level.
This is called Risk Characterisation, which is to compare the amount (concentration) of exposure and quantitativeor qualitative hazard information. When suitable Predicted No-Effect Concentrations (PNECs) or Derived
No-Effect Levels (DNELs) are available, the results are shown by Risk Characterisation Ratios (RCRs) to decide
if risks are adequately controlled. When these no-effect levels cannot be established for certain effects, aqualitative assessment of the likelihood that these effects are avoided when exposure scenarios are implemented
shall be carried out
It is verified that risks are adequately controlled if the results of both hazard assessment and exposure assessment
are reliable, and RCR for all exposure (in all environmental compartments, route, group, and duration) associatedwith all exposure scenarios (ES) and all endpoints is less than 1, or if it is possible to verify by qualitative risk
characterisation that the effects can be avoided when performing ES (See Topic-7). RCR can be obtained with thefollowing formula.

RCR =amount of exposure
PEC
or
PNEC
DNEL

6.2 Procedures for the Risk Characterisation
Risk characterisation is normally conducted as following steps:
Step 0If the substance is classified for physiochemical danger, carry out a risk characterisation
for physicochemical properties.

Step 1

Collect the predicted or derived no-effect levels or minimal effect levels (PNECs,
DNELs or DMELs if appropriate) for the relevant time scales, environmental
ecosystems, human populations, health effects, and routes of exposure. For endpoints
where no DNEL can be derived, collect other information on potency of the substance.

Step 2For each exposure scenario collect the exposure values, measured or estimated, for the
relevant time scales and spatial scales, environmental compartments, human populations
and human routes of exposure.

Step 3Compare matching exposure and predicted or derived no-effect levels or minimal effectlevels for all relevant matching combinations.

Step 4

If no predicted or derived no-effect level or minimal effect level could be derived for a
substance for a certain environmental compartment or human effect, carry out aqualitative risk characterisation for that compartment/effect. This is done if also a PNEC
or DNEL/DMEL is available for other compartments/effects.
Calculate the sum of risk characterisation ratios of combined exposure, e.g. for eachhuman population and for the general population (combined worker and consumer
exposure).
Decide on possible iterations of the CSA, taking uncertainties in the assessment into
account. The risk characterisation should demonstrate control of risks, based on a
sufficiently robust hazard and exposure assessment.

Step 5

Step 6

Step 7

Finalise the risk characterisation.

Procedures related to step 0 to 6 are described below.
346.3 Risk Characterisation for Physicochemical Properties
Substances which are dangerous because of their physicochemical hazard trigger the additional requirements for
the CSR and SDS under REACH in the same way as substances which are dangerous because of their(eco)toxicological properties.
Risk characterisation with regard to human health must be carried out as a minimum for explosivity, flammability
or oxidising potential. For those previously mentioned physicochemical properties, the assessment shall entail anevaluation of the likelihood (risk) that an adverse effect will be caused under the reasonably foreseeableconditions of use in the workplace or by consumers.
The assessment of the potential effects arising from the capacity of hazardous chemical agents to cause accidents,
in particular fires, explosions or other hazardous chemical reactions covers:・ hazards resulting from the physicochemical nature of the chemical agents,
・ risk factors identified in their storage, transport and use, and・ the estimated severity in the event of occurrence.
The accident scenarios to be especially considered linked to REACH are minor accidents which might occur inthe workplace and those related to consumer use. As major accidents caused by chemicals and the requirements tomanage these risks are regulated under the Seveso II Directive (Council Directive 98/82/EC2)12 it can be assumed
that major accident risks are adequately covered at the workplace level.
Independently of the assessment method applied the M/I shall prepare an analysis of the processes and proceduresa hazardous substance is used in and describe the measures taken to prevent accidental release or negative effects
on human health in case of an event. This should include a hazard ranking of the substance (e.g. using theR-phrases as criteria) and a possible frequency and assumed severity of an accident. A rational judgement should
be provided which describes the underlying assumptions and the conclusions made. Based on the assessment one
can either conclude that the use of the substance can be considered of no immediate concern or thatrecommendations for risk reduction are necessary (see CSA Concise Guidance Document Part E.2).

6.4 Risk Characterisation For Human HealthHaving conducted the hazard assessment for all relevant human health endpoints and populations and theexposure estimation; a quantitative, and in some cases also a qualitative, risk characterisation is carried out.
It should be acknowledged that the whole risk characterisation process, whether quantitative or qualitative,
depends heavily upon expert judgment. Therefore, the approach taken in reaching a conclusion needs to be astransparent as possible and needs careful explanation/justification as to assumptions, decisions, uncertainties andadequacy of the available data set.
The risk characterisation for human health is conducted as follows;
1.
2.
3.

Collect and evaluate of all hazard information
Development of exposure scenario and estimation of amount of exposure for all the possible exposure
route
Quantitative and semi- quantitative risk characterisation

The target population exposed are 1) workers, 2) general population (consumers and humans exposed via theenvironment).
The exposure routes of 1) inhalation, 2) dermal, 3) oral are needs to be considered and the risk characterisation
should be carried out for all possible combinations.
The quantitative risk characterisation for human health is conducted as follows:
12
Further guidance see
http://mahbsrv.jrc.it/GuidanceDocs-SafetyManagementSystems.html#Section3-2

35

RCR =

Exposure
DNEL

When RCR < 1, i.e. Exposure < DNEL, → Risk is adequately controlled;
When RCR < 1, i.e. Exposure > DNEL, → Risk is ONT controlled.
If hazards of which threshold (Non-Effect Concentration (Dose)) cannot be established (carcinogenic ormutagenic endpoint, etc.), risk characterisation is performed by using DMEL instead of DNEL. It is concluded
that the risk is controlled if the amount of exposure is smaller than DMEL as similar to the DNEL (See CSA
Concise Guidance Document Part E.3).

6.5 Risk Characterisation for the Environment
Risk Characterisation for the environment is performed by the same method as for human health. Generally,
Predicted Environmental Concentration (PEC) and Predicted Non-Effect Concentration (PNEC) are compared,
and it is considered that the risk is adequately controlled if PEC ＜ PNEC (See CSA Concise GuidanceDocument Part E.2).

Topic-7
Uncertainty Analysis（See CSA In-depth Guidance Document R.19 for details）
In REACH, the risk characterisation is accompanied by uncertainty with the results of RCR calculation,
hazard assessment such as DNEL or PNEC, etc., calculation of PEC or estimated amount of exposure,etc. For instance, if there is no information available when calculating the amount of exposure using an
estimation model, the result obtained by using default values would be more safety side. As a result,the estimated risk may become excessively high. If it is can be demonstrated that risks are adequately
controlled by the RCR obtained in the initial CSA, uncertainty analysis may not be required. However, if
RCR is close to the acceptable border level, or if it is not possible to demonstrate that risks arecontrolled, the collect RCR may be obtained with the uncertainty analysis.
It may be possible to review values which are excessively safety side by re-evaluating the validity of allparameters. At least, it may be possible to avoid conducting unnecessary studies by performing
uncertainty analysis before suggesting or performing collection of additional hazard data.

36

7 Chemical Safety Report (CSR)
7.1 The Standard Format of Contents Included in the Chemical Safety Report (CSR)
According to the CSA Guidance Document, CSR requires to include following items;
1. Conclusions from the CSA. If results were derived by means of quantitative methods, details should bepresented to allow an evaluator to reproduce the results. If results were derived by means of a qualitative(weight of evidence) reasoning, this should be reported.
2. For any endpoints in the hazard or PBT/vPvB sections for which no relevant information is available, therelevant section shall contain the sentence: ‘This information is not available’. In addition, a statement could
be added if the information is not required for a tonnage band or that the results of the CSA do not indicatethat it should be taken into account (e.g., when the CSA does not indicate an exposure-triggered risk to soilorganisms as in REACH Annex X-9.4).
3. For an optional endpoint in the hazard section a statement that the hazard information is required or could be
waived based on the exposure situation. This needs to be argued and documented in a weight of evidence orquantitative reasoning.
4. For any endpoints in Annex IX and X or REACH a testing proposal when needed.
5. The reason why information on specific exposure pathways is not reported. This should be clearly stated andargued. The absence of exposure information need to be argued in order to evaluate if exposure based triggers
have been correctly considered.

7.2 The Format (Template) of Chemical Safety Report (CSR)
The CSR template and explanation of each heading are described in CSA Concise Guidance Document Part F
Appendix.
The REACH registrant must prepare a document following a specific format upon preparation of CSR (SeeTopic-8). The below are the standard headings of CSR.
Title (CHEMICAL SAFETY REPORT)
Substance Name
EC Number
CSA Number
Registrant’s identity
PART A
1. SUMMARY OF RISK MANEGEMENT MEASURES
2. DECLARATION THAT RISK MANAGEMENT MEASURES ARE IMPLEMENTED
3. DECLARATION THAT RISK MANAGEMENT MEASURES ARE COMMUNICATEDPART B
1. IDENTITY OF THE SUBSTANCE AND PHYSICAL AND CHEMICAL PROPERTIES
2. MANUFACTURE AND USE
3. CLASSIFICATION AND LABELLING
4. ENVIRONMENTAL FATE PROPERTIES
5. HUMAN HEALTH HAZARD ASSESSMENT
6. HUMAN HEALTH HAZARD ASSESSMENT OF PHYSICO-CHEMICAL PROPERTIES
7. ENVIRONMENTAL HAZARD ASSESSMENT
8. PBT AND vPvB ASSESSMENT
9. EXPOSURE ASSESSMENT
10. RISK CHARACTERISATION

37

Topic-8
Preparation of CSR Format Using Plug-in Software to IUCLID5
It is being considered in ECHA to add a function with which CSR or OECD SIDS report can be createdautomatically by adding Plug-in Software to IUCLID5. It is expected that the data entered in IUCLID5 areexported in the CSR specific format by using this software. ECHA has announced that they will firstdevelop the software for CSR, which is required for REACH registration, and start the test operation fromaround the end of 2008.
The software will be released at the following ECHA website:
http://echa.europa.eu/reach/software_en.asp

38

8 Safety Data Sheet (SDS)

8.1 Objective of Safety Data Sheet in REACH
The objectives of SDS are to provide easily understandable information on the substance itself or substanceincorporated into preparations to the actors in the supply chain. Since operational conditions (OC) and risk
management measures (RMM) are different based on the condition of use, REACH requires that exposure
scenarios for each of the use or a group of uses needs to be attached as an annex to the SDS.
An immediate downstream user of the registrant should confirm that ES for his own use or his customers use are
relevant to the extended SDS which is provided by M/I. When the substance or the preparation are distributed
further down the supply chain, he should include information on ES included in the extended SDS obtained fromregistrant and other information into his own SDS and provide such information to the customers. In case ES
provided by the registrant do not cover his use or his customers, he should either contact his supplier and ask tohave his use or his customers’use included in an ES or conduct a CSA himself and add the result into his own
SDS for his DUs.
If the immediate DU is the formulator (or re-packer) of an end-use product for down-stream users: The DU is
supposed to extract the relevant information on risk management and OC from the ESs, summarise and include it
in Sections 1.2, 7, 8 and 13 of the SDS for the preparation. The SDS for an end-use product (substance orpreparation) will often address a well defined group of downstream users, and hence the RMM advice does notneed use-specific differentiation. If, however, the same substance/preparation (e.g. a solvent based cleaner) is used
under different operational conditions and/or by means of different RMM, inclusion of the received ES may be
best done by consolidating the received ES into two or more new exposure scenarios annexed to the SDS for the
preparation. This may for example be relevant in situations where a manufacturer or large formulator supplies his
products via distributors and re-packers to end-users (industrial or non-industrial).
If the immediate DU is the formulator of an end-use preparation to be offered or sold to the general public: The
DU is supposed to extract the relevant information on risk management and OC from the received ESs, summarise
and include it in the information for the users (e.g. by means of appropriate use instructions). Such information
shall enable the users of the general public to take the necessary measures as regards the protection of humanhealth, safety and the environment.
Distributors are no downstream users under REACH. Thus, the customer of the distributor is immediate
downstream user next to M/I. It is recommended that M/I actively approach the distributors to seek agreement,
how M/I can increase his knowledge on the conditions of use in the distributor’s market, without requiring the
distributor to disclose confidential business information (CBI). The feedback mechanism may be a suitable way of
doing this, provided the distributor works as a sort of facilitator.

8.2 Requirements for Extended SDS in REACH
Descriptions of the following items are newly required in the SDS based on REACH in addition to the usual(M)SDS. Therefore, this is called Extended SDS (eSDS) in REACH.
・ Assessment results of PBT/vPvB (Persistent, Bioaccumulative / very Persistent, very Bioaccumulative)
・ Predicted No-Effect Concentration (PNEC) for environmental organisms and Derived Non-Effect level(DNEL) for human health・ ES, where risks can be adequately controlled as SDS appendix, and conditions of manufacturing / processing /use included in the ES.

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List of Abbreviations
AC
AF
CMR
CSA
CSR
DMEL
DNEL
DUs
ECHA
ERC
ES
GLP
IU
IUCLID
M/I
NOAEL
OC
PBT
PC
PEC
PNEC
PROC
RCR
RMM
SDS
SIEF
SU
SVHC
vPvB

Article Category
Assessment Factor
Carcinogenic, Mutagenic and Reproductive (toxicant)Chemical Safety Assessment
Chemical Safety Report
Derived Minimal Effect Level
Derived Non-Effect Level
Down Stream Users
European Chemicals Agency
Environmental Release Category
Exposure Scenario
Good Laboratory Practice
Identified Use
International Uniform Chemical Information Database
Manufacturer or Importer
No Observed Adverse Effect Level
Operational Condition
Persistent, Bioaccumulative and Toxic
Chemical Product Category
Predicted Environmental Concentration
Predicted No-Effect Concentration
Process Category
Risk Characterisation Ratio
Risk Management Measure
Safety Data Sheet
Substance Information Exchange Forum
Sector of Use
Substance of Very High Concern
Very Persistent and Very Bioaccumulative40

Useful Links
Contains both English and Japanese materials

ECHA: European Chemicals Agency
http://echa.europa.eu/home_en.asp
ECB: European Chemical Bureau
http://ecb.jrc.ec.europa.eu/reach/
CEFIC: European Chemical Industry Council
http://www.reachcentrum.eu/
Japan Chemical Industry Association
http://www.nikkakyo.org/reach/
Japan Chemical Industry Ecology-Toxicology & Information Center
http://www.jetoc.or.jp/index.html
REACH Center, Japan Environmental Management Association for Industry
http://www.reachcenter.jp/
Network for Strategic Response on International Chemical Management
http://www.chemical-net.info/index.html
Ministry of Economy, Trade and Industry,
http://www.meti.go.jp/policy/chemical_management/int/reach.html
Ministry of the Environment
http://www.env.go.jp/chemi/reach/reach.html

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