Chemical Safety Assessment
Under REACH

Dinant Kroese
TNO| knowledge for businessCONTENTS
1.

Registration requirements

2.

Core tools under REACH

3.

Chemical Safety Assessment (CSA) Human Health4.

Our experience5.

Developments: CSA toolRegistration under REACH
Aim: to ensure that industry adequately manages the risk arising from its substances(starting at 1 tonne/y)Method:– Manufacturer/importer should obtain adequate data
– Provides a registration dossier which includes a chemical safety report (CSR) forsubstances above 10 tonnes/y documenting the Chemical Safety Assessment (CSA)– Submits to authorities (enforcement, transparency)– Increased info requirements according to tonnage (testing proposal)– Reduced requirements for polymers and intermediates

1. Registration requirements:
1. A Technical Dossier
2. A Chemical Safety Report≥ 1 tonne/y≥ 10 tonnes/yFormat of the Technical Dossier----------------------------------------------------------------------------------------------------------------------------------••••••

identity of the Manufacturer / Importer
identity of the substanceinformation on its manufacture and use
the classification and labeling of the substanceguidance on its safe use(robust) study summaries of the information on the intrinsic propertiesof the substance derived from applying Annexes VII to XI• an indication as to whether the above issues and/or, if relevant, the Chemical Safety
Report (→) has been reviewed by an assessor• proposals for further testing, if relevant• between 1 and 10 tonnes, the Techical Dossier shall also contain exposure related
information for the substance (main use categories, type of uses, significant routes ofexposure).

Simplified format of the Chemical Safety Report-----------------------------------------------------------------------------------------------------------------Part A

Summary of risk management measures
Declaration that risk management measures are implemented
Declaration that risk management measures are communicatedPart B

Identity of the substance and physical and chemical properties
Manufacture and uses
Classification and labelling
Environmental fate properties
Human health hazard assessment
Human health hazard assessment of physicochemical properties
Environmental hazard assessment
PBT and vPvB assessment
Chemical Safety Assessment
Exposure assessment
Risk characterization

2. Core tools under REACH• The Chemical Safety Assessment is the tool used to determine thesafety of the chemical• The Chemical Safety Report is the tool used to record/document theassessment to EChA
• The Safety Data Sheet is the tool used to communicate safe use todownstream users (DU)

3. Chemical Safety Assessment, Human HealthAim of the Chemical Safety Assessment:
To establish control of risk for manufacture and use of a substance for all
life-cycle stages.1
Manufacturers/Importers/Downstream Users:
have to ensure that the manufacture and use is in such a way thathuman health and the environment are not adversely affected.

1 on their own or in preparations or in articles

Chemical Safety Assessment should describe:
1. The intrinsic properties of the substance
Human Health (Physico-chemical) hazards
Environmental Health hazards
PBT & vPvB properties

2. All manufacturing and use scenarios

PBT = Persistent, Bioaccumulating and Toxic,
vPvB = very Persistent, and very Bioaccumulating

Note:
If
the substance meets the criteria for classification as dangerous1 or isassessed to be PBT or vPvB,
then
the Chemical Safety Assessment has to include an exposure
assessment for one or more exposure scenario(s), and risk
characterization.
1 i.e. labeled with any R sentenceChemical Safety Assessment should describe:
1. The intrinsic properties of the substance
HH (PC) hazards
ENV hazards
PBT & vPvB properties

2. All manufacturing and use scenarios
3. Risk Characterisation:comparison of ad 1. with exposures of ad 2. (of scenarios, including RMM),
showing control of risk for manufacture & for use

Chemical Safety assessment scheme

Approach to fillrequirements

From REACH Guidance on information
requirements and CSA – Part D

CSA / what intrinsic properties?
of the substance

1. Human health hazard assessment
2. Human health hazard assessment of phys-chem properties
3. Environmental hazard assessment
4. PBT and vPvB assessment

CSA / objectives
1. Human health hazard assessment
1. determine Classification & Labeling in accordance with 67/548/EEC
2. derive Derived No Effect Level (DNEL)

2. Human health hazard assessment of phys-chem properties
1. determine Classification & Labeling in accordance with 67/548/EEC

3. Environmental hazard assessment
1. determine Classification & Labeling in accordance with 67/548/EEC
2. derive Predicted No Effect Concentration (PNEC)

4. PBT and vPvB assessment
1. determine if criteria Annex XIII are fulfilled
2. if yes: characterize emission potential

CSA / evaluation approach
Annex VI

1.

Gather and share available information

2.

Consider information needs

3.

Identify information gaps

4.

Generate new data / propose testing strategy

CSA / evaluation approach
1.

Gather and share available information

All Available Health & Environmental Information:- physico-chemical data
- human data
- in vitro / in vivo data-read-across, SAR, QSAR
&Exposure characteristics
populations & routes
duration
Assessment of reliability, relevance, and adequacy; all within SIEF

CSA / evaluation approach
1.
2.

Gather and share available information
Consider information needs

Adaptations:
Column 2 ofAnnexes VII to X
&Annex XI

CSA / evaluation approach
1.
2.
3.

Gather and share available information
Consider information needs
Identify information gaps

Conclude on whether information is adequate to:assess:&Classification & Labeling,allow the derivation of:
DNEL and PNEC

PBT, vPvB

Coverage of parameters, Weight of the evidence, Transparency; all within SIEF

CSA / evaluation approach
1.
2.
3.

Gather and share available informationConsider information needs
Identify information gaps

In case of inadequate information:

4.

Generate new data / propose testing strategy

1 tpa ≤ Annexes VII & VIII ≤ 100 tpa

100 tpa ≤ Annexes IX & X

CSA / evaluation approach
1.
2.
3.

Gather and share available information
Consider information needs
Identify information gaps

In case of inadequate information:

4.

Generate new data / propose testing strategy

1 Conclude on what exactly is unclear or insufficient
2 Is testing technically possible?
Yes

3 Is exposure-based waiving possible?
No4 Consider if in vitro testing may be adequateNo

5 Conduct or Propose an appropriate in vivo test
I will come back on this≥ 10 tpa: rules in Annex column 2 and Annex XICSA / evaluation approach
1.
2.
3.

Gather and share available information
Consider information needs Provide justification for no testing
Identify information gaps

In case of inadequate information:

4.

Generate new data / propose testing strategy

1 Conclude on what exactly is unclear or insufficientNo

2 Is testing technically possible?
Yes

Yes

3 Is exposure-based waiving possible?
No

4 Consider if in vitro testing may be adequateNo

5 Conduct or Propose an appropriate in vivo test

CSA / evaluation approach
1.
2.
3.

Gather and share available information
Consider information needs
Identify information gaps

In case of inadequate information:

4.

Generate new data / propose testing strategy

Gaps filled?

Chemical Safety assessment scheme

DNEL / DMEL derivation

From REACH Guidance on information
requirements and CSA – Part DQuantitative approach & Qualitative approach
Quantitative approach:- effect-threshold?
→ DNEL (Derived No Effect Level)- no effect-threshold? → DMEL (Derived Minimal Effect Level)
Qualitative approach: infrequently ….
- effect-threshold?
→ e.g. substance is only sensitizer…..
- no effect-threshold? → e.g. mutagen with no cancer data…..

Quantitative approach & Qualitative approach
Quantitative approach:- effect-threshold?
→ DNEL (Derived No Effect Level)- no effect-threshold? → DMEL (Derived Minimal Effect Level)
Qualitative approach: infrequently ….
- effect-threshold?
→ Hazard Banding into ‘High’, ‘Moderate’ &- no effect-threshold? → ‘Low’ → appropriate RMM

Quantitative approach: effect-threshold → DNEL
If applicable:- For every route of exposure / population- Include systemic and local effects ()Quantitative approach: effect-threshold → DNEL
process steps:
Step 1: Derivation of typical dose descriptor(s)(NOAEL, NOAEC, Benchmark Dose, …)
Step 2: Modification of the dose descriptor(s) to thecorrect starting point
Step 3: Application of Assessment factors to thecorrect starting point to obtain the DNEL(s)Step 4: Selection of the leading DNEL/Health EffectQuantitative approach: effect-threshold → DNEL
process steps:
Step 1: Derivation of typical dose descriptor(s)(NOAEL, NOAEC, Benchmark Dose, …)
Step 2: Modification of the dose descriptor(s) to thecorrect starting point
From effectofassessment
datafactorsof the substance
Step 3: Application
Assessment
to thecorrect starting point to obtain the DNEL(s)Step 4: Selection of the leading DNEL/Health EffectQuantitative approach: effect-threshold → DNEL
process steps:
Step 1: Derivation of typical dose descriptor(s)(NOAEL, NOAEC, Benchmark Dose, …)
Step 2: Modification of the dose descriptor(s) to thecorrect starting point
Step 3: Application of Assessment factors to thein bioavailability, route-to-route
correctDifferences
starting point
to obtain the DNEL(s)extrapolation, differences experimental andhuman
exposure
respiratory
Step 4: Selectionof theleadingconditions,
DNEL/Health
Effectvolume corrections

Step 3: Application of Assessment factors to thecorrect starting point to obtain the DNEL(s)Assessment factor

Specifics

Default value

Interspecies

metabolic rate / bw

ASremaining difference
workerconsumersub- to semi
sub- to chronicsemi to chronic

2.5510362

Route-to-routeabsorption

1

Dose response

reliability
L → NOAEL
severity effect1
3
1

Intraspecies
Exposure duration

Quantitative approach: effect-threshold → DNEL
process step:
Step 4: Selection of the leading DNEL/Health Effect• If only threshold effects and DNELs identified…
straightforward selection of the lowest DNEL for a given exposure pattern(population, exposure route, duration, local/systemic);• If also non-threshold effects and DMELs identified… (i.e. mutagenic substance)straightforward selection of the lowest DMEL for a given exposure pattern(population, exposure route, duration, local/systemic);Quantitative approach: no effect-threshold → DMEL
Same process steps:
Step 1: Derivation of typical dose descriptor(s)(T25, BMD10, BMDL10,…. )Step 2: Modification of the dose descriptor(s) to thecorrect starting point
Step 3: Application of Assessment factors to thecorrect starting point to obtain the DNEL(s)Step 4: Selection of the leading DNEL/Health EffectQuantitative approach: no effect-threshold → DMEL
Step 3: Application of Assessment factors to thecorrect starting point to obtain the DNEL(s)Linearised approach
Difference as compared to DNEL approach:•Interspecies
only AS (if oral or dermal)•Intraspeciesno•Duration of exposure yes (in step 2)•Dose-response
sometimes•Quality database
yes+ High to low dose: (e.g.) T25 to 10-5 : 25.000 (linear)Quantitative approach: no effect-threshold → DMEL
Step 3: Application of Assessment factors to thecorrect starting point to obtain the DNEL(s)Large AF approach (~EFSA)
Difference as compared to DNEL approach:•Interspecies
same•Intraspeciessame•Duration of exposure yes (in step 2)•Dose-response
10•Quality databaseno+ Nature of process: 10

SCOEL OELs as DNEL / DMEL
Chapter R8, Appendix 13

If there is an established OEL for the substance, and there isno data since its establishment that is in conflict with this value
this OEL may serve as DNEL or DMEL (for workers)Qualitative approach
Hazard Banding:class

property

RMM / PPE

high

Carc 1,2
Mut 1,2 & 3
Corrosive, strong
Sens (skin, resp.)
Acute tox, very toxic″Very strict″moderate

Carc 3
Corrosive
Sens skin, moderate
Irritating, all targets
Acute tox, toxic″Strict″low

Irritating, single target″Appropriate″Qualitative approach
Hazard Banding:classproperty

RMM / PPE

highCarc 1,2
Mut 1,2 & 3
Corrosive, strong
Sens (skin, resp.)
Acute tox, very toxic″Very strict″

Carc 3
Corrosive
This approach is criticized Sens skin, moderate
for not clearly leading to Irritating, all targets
Acute tox, toxic
moderatedemonstrable ‘control oflowrisk’ or how far should
one Irritating, single target
go with RMM etc.

″Strict″″Appropriate″Risk Characterisation Ratio (RCR)

RCR =Exposure estimate (of ES)DNEL

is determined

If RCR ≤ 1, then there is ‘control of risk’;document and communicate in CSR & SDS+
If RCR > 1, then ‘risks are not controlled’ & assessment needs to be refinedNote: Guidance derivation of DNEL & DMEL: all from animal data
ECETOC and TNO(with an Review Expert Panel from 6 Member State Countries)

have drafted a concept Guidance starting from human data including
an approach how to integrate data from humans and animal, which wasdelivered 2008 to ECHA to finalize.
Expected to be finalized and included in the next Guidance update.

Chemical Safety assessment scheme

From REACH Guidance on information
requirements and CSA – Part DDangerous?

Apply Classification & Labeling Criteria in accordance with Dir 67/548/EEC

Globally Harmonised System of Classification and Labeling of Chemicals (GHS)
Reclassification deadline December 1st 2010
Guidance per this Summer on website ECHAPBT or vPvB ?
Apply assessment criteria:
Parameter

PBT criteria

vPvB criteria

PHalf-life:> 60 d in marine water, or> 40 d in fresh- or estuarine water, or> 180 d in marine sediment or> 120 d in fresh- or est. sediment, or> 120 d in soil

Half-life:> 60 d in marine, freshor estuarine water, or>180 d in marine, freshor estuarine sediment> 180 d in soil

B

BCF > 2000

BCF >5000

T

Chronic NOEC < 0.01 mg/l or C (cat. 1, 2) M (cat.
1, 2) R (cat. 1-3) or ED-effects T-R48 or Xn-R48

Not applicable4. Our experience
1.
2.
3.
4.
5.

Identification leading DNEL is often quite an effort
Case-specifics not always covered by Guidance, so…
When & how ‘Qualitative approach’….??
Some OEL values higher than DNELs……. , and lesstransparant…
Guidance development via ‘learning by doing’ (→ examples!)→ more targeted approaches (DMEL< DNEL)?
How will ECHA respond, what will it accept??

5. Developments: CSA tool

Simple Version: 01/12/09
Extended Version: 01/04/10

Free web based tool for registrants-Extracts relevant information from IUCLID5 (DNELs, R-phrases, physchem data..);-Asks for exposure determinants input from Userto:-Give a 1e tier exposure assessment (with ECETOC TRA model, for w & c)

-Calculates RCR for all relevant scenarios and combinations of applicable routes-If ‘control of risks’:- provides ‘+’ descriptions for SDS+
- documents conclusion in CSR-

If ‘no control of risks’: - indicates that User should perform 2nd tier assessment- asks for result 2nd tier to conclude yes/no ‘control of risks’Thank you for your attention!