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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
4 March 1984 to 18 April 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
17 July 1992
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A pre-existing in vivo skin sensitization study was available.

Test material

Constituent 1
Chemical structure
Reference substance name:
1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylindeno[5,6-c]pyran
EC Number:
214-946-9
EC Name:
1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylindeno[5,6-c]pyran
Cas Number:
1222-05-5
Molecular formula:
C18H26O
IUPAC Name:
4,6,6,7,8,8-hexamethyl-1H,3H,4H,6H,7H,8H-indeno[5,6-c]pyran
Test material form:
liquid: viscous

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Albino Dunkin/Hartley guinea pigs bred in Environmental Safety Laboratory
- Weight at study initiation: (weight 316-350 g)
- Diet (e.g. ad libitum): RGP pellets , hay, cabbage
- Water (e.g. ad libitum): ad libitum

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other:
Concentration / amount:
1) Two 0.1 mL injections of 50% Freund’s Complete Adjuvant (FCA) in 0.9% saline
2) Two 0.1 mL injections of 0.5% Galoxide 50 (equivalent to 0.325% HHCB) in 0.01% DOBS/saline
3) Two 0.1 mL injections of test substance in 0.01 DOBS/saline mixed 50:50 with FCA such that final concentration of test substance was the same as in 2).
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% Galoxide 50 (equivalent to 65% HHCB)
Day(s)/duration:
48 hours (one week after injections)
Challengeopen allclose all
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other:
Concentration / amount:
25% Galaxolide 50 (equivalent to 16.25% HHCB) in vehicle (70% acetone / 30% polyethylene glycol 400 (aceton/PEG400))
Day(s)/duration:
24 hours (14 days after induction)
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
other:
Concentration / amount:
25% Galaxolide 50 (equivalent to 16.25% HHCB) in vehicle (70% acetone / 30% polyethylene glycol 400 (aceton/PEG400))
Day(s)/duration:
24 hours (7 days after first challenge)
No. of animals per dose:
10 (six male, four female)
Details on study design:
RANGE FINDING TESTS:
Several concentrations of the test substance in 0.01% dodecylbenzene sulphonate in 0.9% physiological saline (0.1% DOBS/saline) were injected intradermally to determine a suitable concentration of the test substance for induction of sensitization. Preliminary occluded patch irritation tests were carried out using several concentrations of the test substance in 70% acetone/30% polyethylene glycol (acetone/PEG400) to determine suitable concentrations of a test substance for both induction of sensitisation and for sensitisation challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
Intradermal injections:
1) Two 0.1 mL injections of 50% Freund’s Complete Adjuvant (FCA) in 0.9% saline.
2) Two 0.1 mL injections of 0.5% Galoxide 50 (equivalent to 0.325% HHCB) in 0.01% DOBS/saline.
3) Two 0.1 mL injections of test substance in 0.01 DOBS/saline mixed 50:50 with FCA such that final concentration of test substance was the same as in 2).
Occluded patch application:
- No. of exposures: 1
- Exposure period: 48 hours (one week after injections)
- Site: 2x4 cm clipped and shaved area of the dorsal shoulder
- Concentrations: 100% Galoxide

B. CHALLENGE EXPOSURE
- No. of exposures: 3 (occluded patch application)
- Day(s) of challenge: 7 days after induction, 7 and 14 days after first challenge
- Exposure period: 24 hours
- Concentrations: 25% Galoxide
- Evaluation (hr after challenge): at 24 and 48 hours after removal of the patches
Challenge controls:
Eight animals were treated as controls and received induction and challenge treatments similar to the test pigs minus the test material.
Another four animals were untreated controls for the third challenge only.

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other: 3rd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
None
Reading:
other: 3rd reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
None
Reading:
other: 1st, 2nd and 3rd Reading
Hours after challenge:
48
Group:
positive control
Dose level:
0
No. with + reactions:
0
Total no. in group:
8
Clinical observations:
None
Reading:
other: 1st, 2nd and 3rd Reading
Hours after challenge:
24
Group:
positive control
Dose level:
0
No. with + reactions:
0
Total no. in group:
8
Clinical observations:
None
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25% Galaxolide
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
very faint erythema (score 0.5)
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25% Galaxolide
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
very faint erythema (score 0.5-1)
Key result
Reading:
2nd reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25% Galaxolide
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
very faint erythema (score 0.5)
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25% Galaxolide
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
very faint erythema (score 0.5)
Key result
Reading:
other: 3rd reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25% Galaxolide
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
very faint erythema (score 0.5)
Key result
Reading:
other: 3rd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25% Galaxolide
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
very faint erythema (score 0.5)

Any other information on results incl. tables

At 24 hours, very faint erythema (score 0.5) was found in 2/10 animals at challenge 1, 3/10 animals at challenge 2, and 1/10 at challenge 3. At 48 hours, 3/10, 1/10 and 0/10 had very faint erythema. At challenge at 24 hours, only one animal showed very faint erythema to faint erythema.

Applicant's summary and conclusion

Interpretation of results:
other: Substance is not a skin sensitiser in accordance with EU CLP (1272/2008 and its amendments)
Conclusions:
The substance is not a skin sensitizer in the guinea pig maximization test (OECD guideline 406).
Executive summary:

Test item Galaxolide (65% HHCB in DEP) has been subjected to a guinea pig maximization test (OECD TG 406, non-GLP). The used doses of Galaxolide were 0.5% in 0.01% dodecylbenzene sulphonate in 0.9% saline (DOBS/saline) for the intradermal injection, 100% for the induction patch, and 25% in 70% acetone/30% polyethylene glycol 400 (acetone/PEG400) for the challenge patch. These doses were selected based on preliminary irritation tests using 0.1, 0.25, 0.5, 1.0 and 2.0% Galaxolide concentrations for intradermal injections, however the selection criteria were not clear. The actual concentrations of HHCB are 0.325%, 65%, and 16.25%, respectively. Ten (six male, four female) Albino Dunkin/Hartley guinea pigs (weight 316-350g) were tested on a 2cm x 4cm area of skin in the dorsal shoulder area, clipped and shaved free of fur. Induction consisted of a 0.1 ml intradermal injection of 0.325% HHCB in DOBS/saline and 0.1 ml 50% Freund’s Complete Adjuvant in 0.9% saline. This was followed one week later by a 48 hr occluded patch saturated with 65% HHCB. Challenge applications were made 14 days later with a patch with 16.25% HHCB in 70% acetone/30% PEG 400. Two repeat challenges at weekly intervals were conducted. Observations were made after each challenge at 24 and 48 hours. Eight control animals were received induction and challenge treatments similar to the test pigs minus the test material. At challenge 1, in one animal very faint to faint erythema (score 0.5-1) was noted at 24 hours. In all three challenges three or less per group of ten animals showed very faint erythema (score 0.5) at 24 or 48 hours. There was no evidence of sensitization in any of the guinea pigs at any of the three challenge treatments.