Registration Dossier

Administrative data

Description of key information

There was no indication for skin sensitizing properties of the substance in a vaild guinea pig maximation test according to OECD 406.

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:
from 1982-03-17 to 1982-04-21
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was conducted in 1982, when the GPMT was an internationally accepted and recommended method in order to investigate skin sensitization potential.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Environmental Safety Division, Unilever Research Laboratory, Colworth House, Sharnbrook, Bedfordshire, England
- Weight at study initiation: ca. 320 g
- Diet: ad libitum
- Water: ad libitum
Route:
intradermal
Vehicle:
other: dobs/saline
Concentration / amount:
2 %
Day(s)/duration:
day 0
Route:
epicutaneous, semiocclusive
Vehicle:
other: acetone/PEG
Concentration / amount:
25 %
Day(s)/duration:
day 8
No.:
#1
Route:
epicutaneous, semiocclusive
Vehicle:
other: acetone/PEG
Concentration / amount:
5 %
Day(s)/duration:
day 21 - 22 / 24 h
No.:
#2
Route:
epicutaneous, semiocclusive
Vehicle:
other: acetone/PEG
Concentration / amount:
5 %
Day(s)/duration:
day 28 - 29 / 24 h
No. of animals per dose:
4 males and 6 females (one female was died before the end of the observation period, therefore conclusion is based on 9 animals)
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 pairs of intradermal injections:
two 0.1 mL injections of 50 % Freund's complete adjuvant (FCA),
two 0.1 mL injections of test substance at 2 % (in 0.01 % dobs/saline)
two 0.1 mL injections of test substance in solvent mixed 50/50 with FCA such that the final concentration of test substance injected is 2 % (in 0.01 % dobs/saline)
One week after the injections the same area was exposed as topical application:
A 2x4 cm filter paper patch attached by double-sided adhesive tape to a 4x6 cm piece of thin polyethene, is saturated with the test substance at 25 %(in acetone/PEG) concentration and placed over the shaved site.
- Test groups: one
- Control group:
treated control group: mock induction treatment
untreated control group: no induction
- Site: dorsal shoulder
- Frequency of applications: one week between intradermal injection and topical application

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: 13-14 days after application of the induction patch and one week after the first challenge
- Exposure period: 24 hours
- Test groups: one
- Control group:
treated controls: at first challenge they are treated in exactly the same way as the test animals
untreated controls: at every challenge in the test 4 previously untreated animals of the same sex at challenge are treated in exactly the same way as the test animals
- Site: flank
- Concentrations: 5 % (in acetone/PEG)
- Evaluation (hr after challenge): 24 and 48
Challenge controls:
yes
Positive control substance(s):
no
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
5 %
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
no reaction
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
5 %
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
no reaction
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
other: treated control
Dose level:
5 %
No. with + reactions:
0
Total no. in group:
3
Clinical observations:
no reaction
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
other: treated control
Dose level:
5 %
No. with + reactions:
0
Total no. in group:
3
Clinical observations:
no reaction
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
other: untreated control
Dose level:
0 %
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no reaction
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
other: untreated control
Dose level:
0 %
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no reaction
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
5 %
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
no reaction
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
5 %
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
no reaction
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
other: treated control
Dose level:
5 %
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no reaction
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
other: treated control
Dose level:
5 %
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no reaction
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
other: untreated control
Dose level:
0 %
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no reaction
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
other: untreated control
Dose level:
0 %
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no reaction
Interpretation of results:
GHS criteria not met
Conclusions:
3,5,5-trimethylhexyl acetate is not a skin sensitizer when tested in accordance to the method of Magnusson and Kligman in a guinea pig maximisation test.
Executive summary:

The skin sensitisation potential of the substance 3,5,5-trimethylhexyl acetate (Inonyl acetate) was studied under non-GLP conditions in guinea pigs with a Magnusson-Kligman maximisation test following principles widely similar to those of OECD TG 406. A preliminary irritation test showed that suitably irritant concentration for intradermal induction was 2% of the test item and suitably irritant concentration for induction application was 25% of the test item. The highest non irritant concentration for challenge application was 5% of the test item. Ten albino Dunkin/Hartley strain guinea pigs (4 males and 6 females) were induced for sensitisation via intradermal injection (2%) and one week later by topical application (25%) of the test item. One female guinea pig was killed prior to challenge 1 as it suffered a broken leg. 13 to 14 days after application of the induction patch the animals were challenged (using a dilution containing 5% of test substance) on the clipped and shaved flank by occluded patch. The patch was held in place for 24 hours. The treatment sites were examined for evidence of sensitisation 24 and 48 hours after removal of the patches. One week after the first challenge a second challenge was made on the opposite flank exactly as for the first challenge. Treated and untreated controls were used. Treated controls obtained a mock induction treatment and were challenged exactly the same way as the test animals (5%). Untreated controls were not induced, but challenged in exactly the same way as the test animals. No reaction of sensitisation was observed during both challenges in the examined animals. According to the maximisation test, 3,5,5-trimethylhexyl acetate is not a sensitizer.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The substance was not sensitising to the skin in a valid guinea pig maximisation test following the principles of OECD TG 406. No skin sensitisation potential of the substance was found in two additional in vivo studies with guinea pigs. Hence there is convincing evidence that the substance 3,5,5-trimethylhexyl acetate should be considered as non-sensitising to the skin.


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on skin sensitizing properites the test item is not classified as skin sensitizer according to Regulation (EC) No 1272/2008 (CLP), as amended for the eighth time in Regulation (EU) No 2016/918.