Registration Dossier

Administrative data

Description of key information

SIKA Hardener LH was tested for skin sensitising properties in a guinea pig maximisation test according to EU method B.6 and OECD guideline 406. Based on the results obtained SIKA Hardener LH was considered skin sensitising. There were no indications of respiratory sensitisation from occupational use.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2005-02-16 to 2005-06-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
1996
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1992
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Version / remarks:
1996
Deviations:
no
Principles of method if other than guideline:
NA
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The Guinea Pig Maximazitation Test (2005) met the previous requirements before the entry into force of REACH. The GPMT is suitable and reliable to cover this endpoint. For this reason and for animal welfare reasons, no further in vivo study (LLNA test) needs to be performed.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: LAB-ÁLL Bt. Budapest, 1174 Hunyadi u. 7.
- Age at study initiation: 29 days;
- Weight at study initiation: mean 336.5 grs;
- Housing: macrolon cages, size III., with 3 or 2 animals/cage (42 x 42 x 19 cm);
- Diet: PURISTAR standard diet for rabbits produced by AGRIBRANDS Europe Hungary, 7400 Kaposvár, Dombóvári út, ad libitum.
- Water: tap water, as for human consumption, ad libitum supplemented with 50 mg/100 ml Ascorbic acid.
- Acclimation period: 29 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/- 3 °C
- Humidity: 30-70 % R.H.
- Air changes: 8-12 air exchange/hour by central air-condition system
- Photoperiod: 12 hours daily from 6 a.m. to 6 p.m. (artificial light)

Route:
intradermal
Vehicle:
other: Oleum helianthi
Concentration / amount:
5%
Day(s)/duration:
Day 1
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
other: Oleum helianthi
Concentration / amount:
100%
Day(s)/duration:
Day 8/ 48 hours
Adequacy of induction:
non-irritant substance, but skin pre-treated with 10% SDS
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: Oleum helianthi
Concentration / amount:
100%
Day(s)/duration:
Day 22/ 24 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10 animals in the treatment group;
5 control animals;
Details on study design:
RANGE FINDING TESTS:
A. INTRADERMAL INJECTION
- Concentrations: 0.01, 0.1, 1 and 5% (w/v) in oleum helianthi
- Site: right and left flanks (each 2 concentrations)

B. TOPICAL APPLICATION
- Concentrations: 25, 50, 75% (w/v) in oleum helianthi and undiluted
- occlusive bandage
- two animals were each exposed to two different compounds

Results:
Intra-dermal treatment with test item caused local irritation at concentrations of 1 and 5% up to 48 hours and 24 hours, respectively. At a concentration of 5% well defined erythema occured in both animals one hour after patch removal (score 2). At concentration of 1% well defined and very slight erythema occured one hour after patch removal (score 1). At concentrations of 0.01 and 0.1% no primary irritation was observable (score 0). Topical application of 0.5 mL test formulation at concentrations of 25, 50, 75% and in undiluted state produced no reaction on the skin of guinea pigs (score 0) Therefore, the test item was used at a concentration of 5% for intra-dermal treatment and used in undiluted state for dermal induction treatment and challenge application. The test area was exposed to 0.5 mL of 10% SDS in vaseline 24 hours prior to topical induction applications, in order to create local irritation.

MAIN STUDY
A. 1. INDUCTION EXPOSURE (Injection); Day 1
- No. of exposures: series of three injection to each side (0.1 mL)
- Test groups: 5% test item in oleum helianthi; Freund’s complete adjuvant (FCA) mixed with physiological saline (1:1); 5% test item mixed with physiological saline solution and homogenized in Freund’s complete adjuvant
- Control group: Oleum helianthi; mix of Freund’s complete adjuvant and physiological saline (1:1) (v/v); 50 v/v % oleum helianthi in a 1:1 mixture (v/v) of Freund’s complete adjuvant and physiological saline
- Site: scapular region
- Frequency of applications: once

A.2. INDUCTION EXPOSURE (Epicutaneous); Day 8
- Exposure period: 48 hours
- Test groups: undiluted test item in oleum helianthi
- Control group: oleum helianthi only
- Frequency of applications: once

B. CHALLENGE EXPOSURE (Epicutaneous)
- Day(s) of challenge: Day 22
- Exposure period: 24 hours
- Test groups and control group: undiluted test item (left flank) and vehicle (right flank)
- Site: left shaved flank (undiluted test item), right shaved flank (vehicle only)
- Evaluation (hr after challenge): 24 and 48


Challenge controls:
Concurrent to treatment animals, 5 control guinea pigs were exposed to the vehicle only, during the sensitisation phase, and treated with the test item (in undiluted state) in challenge exposures.
Positive control substance(s):
yes
Remarks:
potassium dichromate
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100%
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
moderate to intense erythema and swelling
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
undiluted
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
moderate to intense erythema and swelling
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
other: control group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
other: control group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
The test item Sika Härter LH (VP) was classified as a skin sensitiser, based on the guinea pig maximisation test and according to current EU-regulations.
Executive summary:

SIKA Hardener LH was tested for skin sensitising properties in a guinea pig maximisation test according to EU method B.6 and OECD guideline 406. A guinea pig maximisation test (GPMT) skin sensitisation study was performed according to the Magnusson and -Kligman method, using Freund's complete adjuvant technique, to evaluate the sensitisation potential of test item SIKA Hardener LH.

A total of 10 test animals were subjected to sensitisation procedures in a two-stage operation, i.e. an intra-dermal treatment and a topical application. The test item was administered at a concentration of 5 % for intra dermal injections and in undiluted state for dermal sensitisation treatments. The test area was painted with 0.5 ml of 10 % sodium dodecyl sulphate in vaseline 24 h prior to the topical induction application in order to create a local irritation. Two weeks following the last induction exposure a challenge dose (in undiluted state) was administered. Challenge was performed by dermal application of the test item.

Concurrent to treatment animals, 5 control guinea pigs were exposed to the vehicle only, during the sensitisation phase, and treated with the test item (in undiluted state) in challenge exposures.

A response, indicating sensitising effects, was observed in 40 % of the treatment group animals after challenge application of the test item. Challenge with the test item elicited intense, confluent erythema and swelling (scores 2-3) in guinea pigs previously sensitized with test item. No response was observed in concurrently challenged control group animals. In summary, SIKA Hardener LH was considered sensitising to skin.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

SIKA Hardener LH was tested for skin sensitising properties in a guinea pig maximisation test according to EU method B.6 and OECD guideline 406. A guinea pig maximisation test (GPMT) skin sensitisation study was performed according to the Magnusson and -Kligman method, using Freund's complete adjuvant technique, to evaluate the sensitisation potential of test item SIKA Hardener LH.

A total of 10 test animals were subjected to sensitisation procedures in a two-stage operation, i.e. an intra-dermal treatment and a topical application. The test item was administered at a concentration of 5 % for intra dermal injections and in undiluted state for dermal sensitisation treatments. The test area was painted with 0.5 ml of 10 % sodium dodecyl sulphate in vaseline 24 h prior to the topical induction application in order to create a local irritation. Two weeks following the last induction exposure a challenge dose (in undiluted state) was administered. Challenge was performed by dermal application of the test item.

Concurrent to treatment animals, 5 control guinea pigs were exposed to the vehicle only, during the sensitisation phase, and treated with the test item (in undiluted state) in challenge exposures.

A response, indicating sensitising effects, was observed in 40 % of the treatment group animals after challenge application of the test item. Challenge with the test item elicited intense, confluent erythema and swelling (scores 2-3) in guinea pigs previously sensitized with test item. No response was observed in concurrently challenged control group animals. In summary, SIKA Hardener LH was considered sensitising to skin.





Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:
There were no indications of respiratory sensitisation from occupational use.

Justification for classification or non-classification

Based on available data on sensitisation properties, Sika Härter LH was classified and labelled as a skin sensitiser cat. 1B (H317: May cause an allergic skin reaction) according to Regulation (EC) No 1272/2008 (CLP).