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Page 1: Potency classification of skin sensitizers (EC WG on ...ec.europa.eu/health/scientific_committees/consumer_safety/docs/... · 2015-07-03 1 2015-07-01 SCCS WG on methodologies 1 Potency

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Potency classification of skin sensitizers

(EC WG on Sensitization)

Carola Lidén, Professor, MD

Carola Lidén

Occupational and environmental dermatology

Clinical, experimental and epidemiological research

Risk assessment tasks

− SCCP member (2004-2009); SCCS external expert (2009-2012)

− OECD Test Guideline: skin sensitization (1992)

− EC WG sensitization: potency (2002-2003)

− OECD WG sensitization: GHS classification (2003-2008)

− ECHA CLP: guidance on application of the CLP criteria (2012-2013)

Funding

- Karolinska Institutet and Stockholm County Council

- Swedish Research Council for Health, Working Life and Welfare

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The clinical disease: allergic contact dermatitis

Clinical tests

Diagnostic

patch test

Baseline

series

Special series,

serial dilutions Repeated open

application (ROAT)

Species Induction /

sensitization

Elicitation / allergic reaction /

disease

Human Skin exposure

(products, mixtures,

articles, etc)

Disease:

− allergic contact dermatitis

Clinical tests:

− diagnostic patch test

− dose-response (ROAT etc)

Guinea pig GPMT, Buehler (subst) Challenge testing

Mouse LLNA (subst) -

Human HRIPT etc Challenge testing (not clinical tests)

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Guinea pig: GPMT, Buehler

Mouse: LLNA

WG sensitization 2002-2003

TC on classification and labelling,

harmonized classification

First question:

Propose how to use the existing

methods in order to grade allergen

potency, providing detailed guidance

for current predictive test methods

The approach has been introduced

in GHS and CLP

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Potency categorization of classified skin sensitizers

based on LLNA

EC3 value

(%)

EC WG sens

& SCCP

CLP & GHS

(H317 former

R43)

EC3 value

(%) ECETOC

≤0.2 extreme 1A <0.1 extreme

>0.2 - ≤2 strong 1A ≥0.1 - <1 strong

>2 moderate 1B ≥1 - <10 moderate

≥10 - ≤100 weak

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EC3 value: the amount of a chemical that is required to elicit a three-fold

increase in lymph node cell proliferative activity (SI ≥ 3)

Basketter et al 2005; SCCP 2005; Guidance on the Application of the CLP Criteria ver 4 2013;

GHS 5th rev 2013; ECETOC 2003

Potency categorization based on GPMT or Buehler Test

Categorization is based on

- intradermal induction concentration in the GPMT

- topical induction concentration in the Buehler test

Methods designed for assessment of sensitization potential (yes or no),

not potency

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How to deal with discrepancies

When EC3 values are available from more than 1 study, the

lowest value should normally be used

Where multiple animal data sets lead to different categorization of

the same substance, the higher potency category should apply

Human data may indicate the need to change the potency

categorization derived from animal experiments. Normally, only

for re-categorization into a higher potency category

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Basketter et al 2005

Submissions to SCCP often insufficient

LLNA

- Conc: too low, too high, too narrow span

- Vehicle: inadequate, not prio

GPMT

- Conc: too low for induction, challenge

- Often no dose-range-finding test

SCCP conclusions often inconsistent

SCCP memorandum

- OECD TG requirements

- Potency categories

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Memorandum on hair dye substances and their skin

sensitising properties. SCCP 19 December 2006

Memorandum on hair dye chemical sensitisation.

SCCS 26 February 2013

Opinion on fragrance allergens in cosmetic products.

SCCS 26-27 June 2012

Other SCCP and SCCS opinions

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Yazar et al, manuskript

Skin

sensitizing

potency

according to

LLNA (EC3)

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2.0

0.2 Cinnamal

HICC

Citronellol

Formald

MDBGN

MCI/MI

MI

BIT

Imidurea

PPD

TDA

npPPD

2mRes

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Conclusions

The categorization in the SCCP memorandum was recently

implemented in GHS and CLP

Animal tests will continue to be important for SCCS

- LLNA and GPMT. Modifications may give more information

Human data on elicitation

-Elicitation thresholds are much lower and correlate poorly with

induction potency

- Essential basis for prevention of clinical disease

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