LCID Methodology - Human Health Hazards

LCID Methodology - Human
Health Hazards
Cefic/VCI Workshop on the LCID methodology
Marius Arndt, Marc Brulport, Frank Schnöder and Stefanie Welz
4 May 2016
Content
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General principles of LCID Methodology
Explanation of the workflow – best case
YOUR TURN: Example
Backup approach
YOUR TURN: Example
Special cases
YOUR TURN: Example
Communication of results
Excel based calculation tool
04 May 2016
LCID Methodology
2
General principles of LCID methodology
1. Identify components of the mixture and collect relevant data available
for the assessment of the mixture such as CLP classification,
concentration, reference values; consider cut-off criteria
2. Carry out CLP classification of the mixture
3. Identify relevant components:
a. Priority substances (carcinogen or mutagen) present above
threshold levels?
b. Lead components per route of exposure
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LCID Methodology
3
General principles of LCID methodology
3. Identify relevant components:
a. Priority substances (carcinogen or mutagen) present above
threshold levels?
b. Lead components per route of exposure
4. a. Collect required exposure scenario information for priority
substances. Priority substances usually require the most stringent
operational conditions (OC) and risk management measures (RMM).
Note: If the priority substance only causes effects via one route of
exposure consider identification of lead components for other routes of
exposure.
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LCID Methodology
4
General principles of LCID methodology
3. Identify relevant components:
a. Priority substances (carcinogen or mutagen) present above
threshold levels?
b. Lead components per route of exposure
4. b. Identify the Lead Components; for each component driving a hazard
classification of the mixture, calculate its Lead Component Indicator
(LCI) by:
Ci
𝐿𝐶𝐼 =
DNEL
with Ci being the concentration of component i in the mixture and
DNEL being the derived no-effect level
The highest LCI for each exposure route is the Lead Component.
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LCID Methodology
5
General principles of LCID methodology
5. Identify any components which drive any local effects
(for human health)
6. Collect required information OCs and RMMs for Priority
Substances/Lead Components/ components driving local effects;
consolidate to derive safe use information for the mixture
7. Generate safe use information. Decide whether to include it in sections
1 to 16 or to develop an annex to the safety data sheet
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LCID Methodology
6
General template
Information to be collected beforehand in order to be
able to run the LCID Methodology, e.g. classification
or DNEL values
Result of calculations (e.g., LCI) or documentation of
conclusions drawn (e.g., relevant local effects or is
there a priority substance present)
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LCID Methodology
7
General template
If applicable, present the results of grouping and
calculation of weighted concentration of components
Identify relevant components with missing DNELs
Entry parameters for backup-approach, if applicable.
Results of backup-approach, if applicable. Both
NOAEL/NOAEC and LD50/LC50 possible.
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LCID Methodology
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General template
Entry parameters for backup-approach, if applicable.
Results of backup-approach, if applicable. Both
NOAEL/NOAEC and LD50/LC50 possible.
Operational conditions and risk management
measures per component and per identified use.
Modified operational conditions and risk
management measures for the mixture
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LCID Methodology
9
LCID workflow – DNELs available
Given scenario
• REACH relevant data on components is available
• Mixture is classified as hazardous
according to CLP (for both systemic and local
effects)
• Interaction between chemicals is not
suspected
• Data on mixture as a whole is not available
• No priority substance above CLP cut-off limits
present in the mixture
• DNELs are available for all relevant
components
• No potential exposure to vapors at room or
process temperature
• Grouping of effects using LCID methodology
will be demonstrated separately
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LCID Methodology
10
LCID workflow step by step - DNELs
1
Compile REACHrelevant product data
Here it is assumed that
relevant data is available,
e.g. classification and
composition of mixture,
classification of
components, DNELs etc.
Is the mixture
classified as
hazardous?
2
Here the mixture is
assumed to be classified
as hazardous according
to CLP
YES
Is the mixture
classified as hazardous
to Human Health?
H1
Mixture is assumed to be
classified for both local
and systemic effects on
human health
YES
Is interaction
between chemicals
suspected?
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LCID Methodology
H2
NO
Interaction is not
expected
Cont’d on next slide
11
LCID workflow step by step - DNELs
Is HH toxicity data
available on the
mixture as a whole?
There is no data
available on the
mixture as a
whole
In this example no
priority substance
is present above
CLP cut-off limits
H4
Is the mixture only
classified for local
effects?
Mixture is also
classified for
systemic effects
NO
Are any of the
components identified
as a priority
substance?
There is a
reference value
for each
component
driving C&L
NO
H6
Identify relevant components which
contribute to the hazard of the mixture
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NO
Are there reference
values available for
relevant components?
H5
H6a
H7
YES
H8
Is there potential for
exposure to vapors?
No potential
exposure to
vapors either at
room or process
temperature
LCID Methodology
NO
Cont’d on next slide
12
LCID workflow step by step - DNELs
H9
Calculate the LCI for all relevant exposure routes
𝐿𝐶𝐼 =
Ci
DNEL
With Ci being the concentration of component i
in the mixture and DNEL being the relevant
derived no-effect level
Are DNELs available
for all relevant
components?
In our case DNELs
are available for
all relevant
components
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Compile OCs and RMMs for each exposure
route based on the lead component (LC) H15
per relevant contributing activity
Consider local effects for each exposure
route
H16
If needed, compile OCs and RMMs based
H17
on local effects (e.g., eyes, skin,
respiratory tract)
H12
Identify OCs and RMMs to derive safe use
H18
information for mixture per exposure
scenario and contributing activity
YES
Steps H10 and H11 are
not relevant in this example
Provide safe use information either
embedded within SDS or as an annex to
SDS
LCID Methodology
H19
13
DNEL example – your turn!
CLP Health Hazard Classification H302: Harmful if swallowed
of mixture
H314: Causes severe skin burns and eye damage
H336: May cause drowsiness and dizziness
H370: Causes damage to organs
Component 1
Component 2
Relevant components
30
34
Concentration
Addendum: According to REACH article
14(4) ES information might not be available
for substances solely classified for narcotic
effects (H336)
Component 3
36
Health Hazard CLP classification H302: Harmful if swallowed
H336: May cause drowsiness or
H370: Causes damage to organs dizziness
H314: Causes severe skin burns
and eye damage
DNEL inh (mg/m³)
10
15
120
DNEL derm (mg/kg bw day)
40
30
120
not relevant
not relevant
Indoor with LEV;
5 days per week; > 4 hrs/day
Wear chemically resistant gloves
(tested to EN374) in combination
with ‘basic’ employee training.
Indoor w/o LEV
5 days per week; > 4 hrs / day
Safety goggles; Wear suitable
gloves tested to EN374.
Vapour Pressures @ 25°C (hPa) not relevant
Contributing Scenario
Operating Conditions (OCs)
Risk Management Measures
(RMMs)
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PROC 8a
Indoor with LEV
5 days / week; < 4hrs/day
Wear suitable gloves tested to
EN374.
LCID Methodology
14
DNEL example – calculations
Calculate the LCI for all relevant exposure routes
𝐿𝐶𝐼 =
Ci
DNEL
With Ci being the concentration of component i
in the mixture and DNEL being the relevant
derived no-effect level
Component 1
Component 2
𝐿𝐶𝐼𝑖𝑛ℎ𝑎𝑙𝑎𝑡𝑖𝑜𝑛 =
30
= 3,0
10
𝐿𝐶𝐼𝑖𝑛ℎ𝑎𝑙𝑎𝑡𝑖𝑜𝑛 =
34
= 2,3
15
𝐿𝐶𝐼𝑑𝑒𝑟𝑚𝑎𝑙 =
30
= 0,8
40
𝐿𝐶𝐼𝑑𝑒𝑟𝑚𝑎𝑙 =
34
= 1,1
30
• Component 1 is the lead component via inhalation
• Component 2 is the lead component via dermal route of exposure
• Component 3 is classified for local hazards only hence no LCI calculation
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LCID Methodology
15
DNEL example – results
only for demonstration purposes
CLP Classification of the mixture
Relevant components
Concentration
Health Hazard CLP classification
H302; H314; H336; H370
Component 1
30
H302: Harmful if swallowed
H370: Causes damage to organs
Component 2
34
H336: May cause drowsiness or dizziness
Relevant local effects
Health Hazard Priority Substance
(yes/no)
DNEL inh (mg/m³)
DNEL derm (mg/kg bw day)
Vapour Pressures @ 25°C (hPa)
LCI (DNEL) - inh
LCI (DNEL) - derm
Are there DNELs available for all the
relevant components? (yes/no)
Lead Component
Contributing Scenario
Operating Conditions (OCs)
H314: Causes severe skin burns and
eye damage
No
No
No
10
40
not relevant
3,0
0,8
15
30
not relevant
2,3
1,1
120
120
not relevant
0,3
0,3
Yes
Yes
Yes
LC for dermal route of exposure
Local effects (dermal and eye)
Indoor with LEV;
5 days per week; > 4 hrs/day
Wear chemically resistant gloves (tested
to EN374) in combination with ‘basic’
employee training.
Indoor w/o LEV
5 days per week; > 4 hrs / day
Safety goggles; Wear suitable gloves
tested to EN374.
LC for inhalation
PROC 8a
Indoor with LEV
5 days / week; < 4hrs/day
Risk Management Measures (RMMs) Wear suitable gloves tested to EN374.
Modified OCs for the Mixture
Modified RMMs for the Mixture
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Component 3
36
H314: Causes severe skin burns and
eye damage
Indoor with LEV; 5 days / week; < 4hrs/day
Safety goggles; Wear chemically resistant gloves (tested to EN374) in combination with ‘basic’ employee training.
LCID Methodology
16
Backup approach
• in case DNELs are missing for one component
• calculation of LCCIs (Lead Component Candidate Indicator) using
NO(A)EL/NO(A)EC/ATE/LD50/LC50 (section 11 SDS main body)
• LCCI is calculated per component and per route of exposure
• any comparison must be made on an equivalent basis, e.g. NO(A)ELs with
NO(A)ELs etc.
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LCID Methodology
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Backup approach – work flow part 1
Backup approach
work flow
H13
Are there NO(A)EL or NO(A)EC
values available?
YES
Calculate LCCI for each relevant component
for each exposure route. Ensure NO(A)EL or
NO(A)EC values are for same species, via the
same exposure route and duration:
Cont’d on next slide
04 May 2016
NO
H13a
H13b
Calculate LCCI for each relevant component
for each exposure route based on LD50 or
LC50 or ATE values:
LCID Methodology
18
Backup approach – work flow part 2
H14
Is there any DNEL available for the
component with the highest LCCI
per exposure route?
NO
YES
H15
Compile OCs and RMMs for each exposure route
based on the LC(s) per relevant contributing
activity (PROC)
H16
Consider local effects for each exposure route
(eyes/skin/resp.irritation,corrosivity,skin/inhalation
sensitisation)
If needed, compile OCs and RMMs based on local
effects (eyes,skin,respiratory tract)
H17
Identify OCs and RMMs per Exposure Scenario and
Contributing Activity to derive safe use information
for mixture
H18
Safe use information must be derived on a caseby-case basis
H3
Provide safe use information either embedded
within SDS or as an annex to SDS
H19
Document. Go to ENV hazard workflow E1
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LCID Methodology
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19
Backup example – Your turn!
CLP Health Hazard Classification H302: Harmful if swallowed
of mixture
H314: Causes severe skin burns and eye damage
H336: May cause drowsiness or dizziness
H370: Causes damage to organs
Component 1
Component 2
Relevant components
30
34
Concentration
Component 3
36
Health Hazard CLP classification H302: Harmful if swallowed
H336: May cause drowsiness or
dizziness
H314: Causes severe skin burns
and eye damage
H370: Causes damage to organs
DNEL inh (mg/m³)
15
10
10
15
No DNELs!
DNEL derm (mg/kg bw day)
NOAEC inh (mg/m³)
80
150
200
NOAEL derm (mg/kg bw day)
200
100
200
Contributing Scenario
Operating Conditions (OCs)
Not available
Not available
Risk Management Measures
(RMMs)
Not available; consideration of
section 8 of MSDS for PPE
possibly: e.g. respiratory
protection according to EN140
PROC 8a
Indoor w/o LEV;
5 days per week; > 4 hrs/day
Wear chemically resistant gloves
(tested to EN374) in combination
with ‘basic’ employee training.
Indoor with LEV;
5 days per week; < 4 hrs/day
Safety goggles; Wear suitable
gloves tested to EN374.
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LCID Methodology
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Backup example – calculations
Component 1:
Component 2:
Component 3:
!
!
• Lead component inhalation: not determinable, Comp.1 highest LCCI (inh), no DNELs,
LCI(inh) Comp.3 higher than LCCI(inh) Comp.1
case-by-case decision, please refer to step H3 of workflow, expert judgement necessary
• Lead component dermal: Comp.2, highest LCCI(derm) and LCI(derm)
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LCID Methodology
21
Backup example – results
only for demonstration purposes
CLP Classification of the mixture
Relevant components
Concentration
Health Hazard CLP classification
H302; H314; H336; H370
Component 1
30
H302: Harmful if swallowed
Component 2
34
H336: May cause drowsiness or dizziness
Relevant local effects
Health Hazard Priority Substance
(yes/no)
DNEL inh (mg/m³)
DNEL derm (mg/kg bw day)
NOAEC inh (mg/m³)
NOAEL derm (mg/kg bw day)
LCI (DNEL) - inh
LCI (DNEL) - derm
Are there DNELs available for all the
relevant components? (yes/no)
LCCI (NOAEC) – inh
LCCI (NOAEL) - derm
Lead Component
Contributing Scenario
Operating Conditions (OCs)
H314: Causes severe skin burns and
eye damage
No
No
No
80
200
Not available
Not available
15
10
150
100
2,3
3,4
10
15
200
200
3,6
2,4
No
Yes
Yes
0,2
0,3
LC for dermal route of exposure
PROC 8a
Indoor w/o LEV
5 days per week; > 4 hrs / day
Risk Management Measures (RMMs) Not available; consideration of section 8 Wear chemically resistant gloves (tested
of MSDS for PPE possibly: e.g.
to EN374) in combination with ‘basic’
respiratory protection according to
employee training.
EN140
Modified OCs for the Mixture
Modified
RMMs
for the Mixture
04 May
2016
Component 3
36
H314: Causes severe skin burns and
eye damage
H370: Causes damage to organs
0,4
0,2
Not determinable
Not available
Not available
0,2
0,2
Local effects (dermal and eye)
Indoor with LEV
5 days per week; < 4 hrs / day
Safety goggles; Wear suitable gloves
tested to EN374.
Indoor with LEV; 5 days / week; < 4 hrs/day (worst-case assumption)
Respiratory protection according
to Methodology
EN140; Safety googles; Wear chemically resistant gloves (tested to EN374) in
LCID
combination with ‘basic’ employee training.
22
Grouping
•
To be considered, if components act via same mode of action
•
In the absence of better knowledge, it is suggested to apply grouping to
•
–
acute toxic effects (e.g., for inhalation group substances with: H330, H331, H332)
–
drowsiness and dizziness
Follow the same steps as before until calculation of the LCI values
Mixture classified as
hazardous to Human
Health?
H1
Identify relevant components which
contribute to the hazard of the mixture
H9
YES
H5
Priority substance
present?
NO
04 May 2016
H6
Calculate the LCI for all exposure routes
Ci
𝐿𝐶𝐼 =
DNEL
With Ci being the concentration of component
i in the mixture and DNEL being the relevant
derived no-effect level
LCID Methodology
23
H10 – H11
Grouping - Workflow
NO
YES
Identify components with
similar mode of action
Calculate the LCI for the group
(separately per route)
𝑛
𝐿𝐶𝐼𝑔𝑟𝑜𝑢𝑝 =
𝐿𝐶𝐼𝑖
Component with
highest LCI is lead
component
Continue as without
grouping
Component with highest
LCI within the group is
lead component
Adjust concentration
𝑛
𝑖=1
𝐶𝑤𝑒𝑖𝑔ℎ𝑡𝑒𝑑 =
𝑖=1
𝐶𝑖 ∗ 𝐷𝑁𝐸𝐿𝐿𝐶
𝐷𝑁𝐸𝐿𝑖
LC : Lead component
i: all members of the group
LCIgroup largest
LCI?
Select appropriate RMMs
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LCID Methodology
24
Grouping example
CLP Health Hazard Classification of
mixture
H331: Toxic if inhaled
H311: Toxic in contact with skin
H301: Toxic if swallowed
H315: Causes skin irritation
Component 1
5
H336: May cause drowsiness or dizziness
H373: May cause damage to organs through prolonged or repeated exposure
H361d: Suspected of damaging the unborn child
Component 2
30
Component 3
65
Health Hazard CLP classification
H225; Flam. Liq. 2
H315; Skin Irrit. 2
H336; STOT SE 3 (narcotic)
H225; Flam. Liq. 2
H361d; Repr. 2;
H373; STOT RE 2 (inhal)
H311; Acute Tox 3 (dermal)
DNEL inh (mg/m³)
260
192
H301; Acute Tox 3 (oral)
H311; Acute Tox 3 (dermal)
H331; Acute Tox 3 (inhal)
H373; STOT RE 2
H336; STOT SE 3 (narcotic)
8
DNEL derm (mg/kg bw day)
40
384
1,23
Vapour Pressures @ 25°C (hPa)
not relevant
not relevant
not relevant
Contributing Scenario
Proc 8a
Operating Conditions (OCs)
5 days per week; > 4h per day
5 days per week; 8h per day
5 days per week; 8 h per day
Relevant components
Concentration
Risk Management Measures (RMMs) Provide local exhaust ventilation 90%
Provide a good standard of general
Provide local exhaust ventilation 90%
ventilation (at least 3 to 5 air changes per
hour) or wear a respirator conforming to
EN140 with type A filter or better
Wear gloves (TypeEN374)
04 May 2016
Wear suitable gloves tested to EN374.
LCID Methodology
25
Grouping example
only for demonstration purposes
CLP Classification of the mixture
Relevant components
Concentration
Health Hazard CLP classification
H331, H311, H301, H336, H373, H315, H361d
Component 1
Component 2
5
30
H225; Flam. Liq. 2
H225; Flam. Liq. 2
H315; Skin Irrit. 2
H361d; Repr. 2;
H336; STOT SE 3 (narcotic)
H373; STOT RE 2 (inhal)
H311; Acute Tox 3 (dermal)
Relevant local effects
DNEL inh (mg/m³)
DNEL derm (mg/kg bw day)
LCI (DNEL) - inh
LCI (DNEL) - derm
Grouping - inhalation
LCI Grouping (DNEL) inh
Cweighted of LC - inh (%)
Grouping - dermal
LCI Grouping (DNEL) dermal
Cweighted of LC - dermal (%)
Lead Component
Contributing Scenario
Operating Conditions (OCs)
Risk Management Measures (RMMs)
Skin Irrit. 2
260
40
0,02 (Concentration / DNEL)
0,13 (Concentration / DNEL)
Yes, inhalation (H336)
8,1 (LCI Comp. 1 + Comp. 3)
None
192
384
0,16
0,1
No, inhalation
Yes, dermal (H336)
52,93
Yes, dermal (H311)
52,9
Modified OCs for the Mixture
Modified RMMs for the Mixture
5 days per week; ≤8 h per day
Provide local exhaust ventilation (LEV) 90% +Wear gloves (TypeEN374)
04 May 2016
Proc 8a
5 days per week; > 4h per day
Provide local exhaust ventilation 90%
Wear gloves (TypeEN374)
Component 3
65
H301; Acute Tox 3 (oral)
H311; Acute Tox 3 (dermal)
H331; Acute Tox 3 (inhal)
H373; STOT RE 2
H336; STOT SE 3 (narcotic)
None
8
1,23
8,13
52,8
Yes, inhalation (H336)
8,1 (H336)
65+5*8/260 = 65,2 (H336)
Yes, dermal (H311, H336)
52,9 (H311) / 52,93 (H336)
65+5*1,23/40 = 65,2 (H336)
Lead Component (inhal. and dermal)
5 days per week; 8h per day
5 days per week; 8 h per day
Provide a good standard of general
Provide local exhaust ventilation 90%
ventilation (at least 3 to 5 air changes per Wear suitable gloves tested to EN374.
hour) or wear a respirator conforming to
EN140 with type A filter or better
LCID Methodology
26
Priority substances
• Scenario: Mixture contains a priority substance (Carcinogen or Mutagen)
 Collect RMMs from priority substance
 Check, if other components are classified for local effects
 Add RMMs for local effects, if needed
• Special example:
Priority substance classified to cause cancer only via inhalation
 Follow the steps above, but only use inhalation RMMs from the priority substance
 Perform LCID calculation for remaining routes (include priority substance in calculation)
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LCID Methodology
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Priority substances
• Why are substances classified as toxic to reproduction not treated as
priority substances?
– Priority substances
• non-threshold effects
• RMMs designed to minimize exposure as much as possible
– Reproductive toxicity
• DNELs available
• RMMs not necessarily strict enough to cover risk of all other components
 comparison of all components necessary
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LCID Methodology
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Safe use information for mixtures
•
•
In the examples, RMMs were only collected for one PROC
In reality, RMMs need to be collected for every use of the mixture
Repeat for each PROC
Option 1:
Generate an Annex to the mixture SDS and provide information for each use
CS* LS inhalation
CS* LS dermal
local effects
OCs
RMMs
worst case
OCs
RMMs (inhal.)
RMMs (derm.)
SDS Product (Annex)
* Contributing
04 May 2016
scenario
OCs
RMMs
LCID Methodology
29
Safe use information for mixtures
Repeat for each PROC
Option 2: Combine information for all uses in the main part of the SDS
CS LS dermal
CS LS inhalation
OCs
worst case
local effects
OCs
RMMs
RMMs (derm.)
RMMs (inhal.)
OCs
RMMs
select worst case
(limited option to
separate per use)
select worst case
SDS Product (Section 7/8)
OCs
04 May 2016
RMMs
LCID Methodology
30
The LCID (calculation) Tool
• An Excel based LCID tool was developed primarily for „proof of concept“
and facilitating routine calculations considering the LCID rules
• The scope of the LCID Tool is limited to the identification of the
LCs/LCCIs/Priority substances and the related Cweighted and MF values
 consolidation of RMMs is NOT included and needs be done
outside of the Tool
• Tool contains some “in-tool“ guidance and support for users
– Permanent and conditional text messsages
– Comments on individual cells
• Tool contains macros to
– clear all entries
– populate parts of the main sheet with data generated in supporting sheets
e.g. after unit conversion for DNELs or calculation of lowest PNEC
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LCID Methodology
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The LCID (calculation) Tool - Overview
• Excel template has the following sheets
– “Disclaimer“ and “Short_Instructions“ sheets => for information
PLEASE READ carefully !! - Short instructions are essential for use of Tool!
– “LCID“ sheet is main sheet for user
– “PNEC“ sheet allows calculation of critical PNEC for components =>
population of LCID
– “unit conversion inhalation“for unit conversions => population of LCID
– “SCL“ for entry of Specific Concentrations Limits => will be used in logic if
entered
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LCID Methodology
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The LCID Sheet - Overview
Administrative data
Outcome
Input for mixture
Remark: Input for individual components extends further to right in the tool => => =>
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LCID Methodology
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The Workshop Examples in the LCID Tool
• Let‘s go !
Workshop examples
I. LCID Workshop Example HH DNEL
II. LCID Workshop Example HH Backup
III. LCID Workshop Example HH Grouping
DNEL
Concentration
Classification
LCs per route for mixture
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LCID Methodology
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