Calcium 3,5,5-trimethylhexanoate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Principles of method if other than guideline:

No test guideline stated, but the method used is similar to OECD TG

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

A LLNA assay does not need to be conducted, since adequate information from an other in vivo study are already available.

Test material

Test material information

Constituent 1

Reference substance name:

Fatty acids, C9-13-neo-

EC Number:

273-114-3

EC Name:

Fatty acids, C9-13-neo-

Cas Number:

68938-07-8

Molecular formula:

C9H18O2 to C13H26O2

IUPAC Name:

Fatty acids, C9-13-neo-

Constituent 2

Reference substance name:

Fatty acids, C9-13-neo-

Cas Number:

68938-07-8

IUPAC Name:

Fatty acids, C9-13-neo-

Details on test material:

- Name of test material (as cited in study report): Versatic 913D, versatic 913 disstillate, C9-C13 neo acid mixture
- Substance type: carboxylic acid, mixture of neo-acids
- Physical state:clear pale yelow liquid
- Analytical purity: see below
- Composition of test material, percentage of components:
Versatic 5 content 0.8 % m/m
Versatic 6 content 5.8 % m/m
Versatic 7 content 6.2 % m/m
Versatic 9 content 70.0 % m/m
Versatic 10 content 0.9 % m/m
Versatic 11 content 0.2 % m/m
Versatic 13 content 6.9 % m/m
Greater than Versatic 13 3.2 % m/m
Versatic 9 isomers 43.9 % m/m
Water 0.14 % m/m
Acid value 346 mgKOH/g
Density (20°C) 0.922 kg/L
- Purity test date: 1993-05-18
- Lot/batch No.:Tank No. 1537; Ident 9450/9F09
- Stability under test conditions: stable
- Storage condition of test material: at ambient temperature in the dark

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: Harla Porcellus
- Age at study initiation: 7 to 11 weeks
- Weight at study initiation: males 560 - 702 g; females 487 - 602 g
- Housing: single sex groups of up to five animals were housed in hanging stainless steel cages (62 x 62 x 25 cm) with wire-mesh floors; trays for excreta lined with absorbant pads were placed beneath each cage.
- Diet (e.g. ad libitum): pelleted diet (FD1, S.Q.C., Special Diets Services Ltd.), ad libitum
- Water (e.g. ad libitum): water from public supply, ad libitum
- Acclimation period: at least 16 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 23
- Humidity (%): 30 to 70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): fluorescent lighting; 12 / 12 h

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

corn oil

Induction 2

Concentration / amount:

Induction, intradermal: 2% m/v Versatic 913D in corn oil
topical: undiluted (pure) Versatic 913D
Challange, topical: undiluted (pure) Versatic 913D

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

corn oil

Challenge 2

Concentration / amount:

Induction, intradermal: 2% m/v Versatic 913D in corn oil
topical: undiluted (pure) Versatic 913D
Challange, topical: undiluted (pure) Versatic 913D

No. of animals per dose:

20 (10 males, 10 females)

Details on study design:

RANGE FINDING TESTS: 2 male und 2 female animals were used. For intradermal induction, concentrations of 0.06, 0.2, 0.6, and 2.0 % m/v test substance in corn oil were tested. For topical application, dilutions of 10%, 25%, and 60% in corn oil (m/v) as well as undiluted (pure) test substance were tested.
After intradermal injection of up to 2% test solution, dermal reactions did not exceed slight redness (3 animals) or pink/red areas (one animal) of the injection site. After topical application of pure test substance, there was no dermal reaction.
2.0% test substance in corn oil for intradermal injection and pure test substance for topical application were selected as test concentrations.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal injection and topical application)
- Exposure period: topical application: 48 h
- Test groups: intradermal injection: 0.1 mL of a 50% aqueous emulsion of FCA, 0.1 mL of TS in vehicle (0.2% w/v in corn oil), 0.1 mL of TS in FCA; topical application: 0.3 mL of TS soaked on filter paper (16 cm²), occlusive wrapping
- Control group: intradermal injection: 0.1 mL of FCA, 0.1 mL of vehicle, 0.1 mL of vehicle in FCA; topical application: vehicle soaked on filter paper (16 m²), occlusive wrapping
- Site: shoulder region; either side of the mid-line
- Frequency of applications: 2 applications, topical induction was applied seven days after intradermal injection.
- Duration: total of three weeks
- Concentrations: 2% TS in corn oil and pure TS, respectively (see above)

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (three weeks after start of induction - intradermal injection)
- Day(s) of challenge: 1
- Exposure period: 24 h
- Test groups: 0.1 mL of pure TS on filter paper (16 m²)
- Control group: 0.1 mL of pure TS on filter paper (16 m²)
- Site: on one flank of test animals
- Evaluation (hr after challenge): shortly, 24 h and 48 h after removal of the challenge patches

Positive control substance(s):

not specified

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

Not specified

No. with + reactions:

0

Total no. in group:

0

Clinical observations:

Not specified

Remarks on result:

not measured/tested

Results 2

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

not specified

No. with + reactions:

0

Total no. in group:

0

Clinical observations:

Not specified

Remarks on result:

not measured/tested

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

2.0% in corn oil and pure test substance

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 2.0% in corn oil and pure test substance. No with. + reactions: 0.0. Total no. in groups: 20.0.

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

2.0% in corn oil and pure test substance

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 2.0% in corn oil and pure test substance. No with. + reactions: 0.0. Total no. in groups: 20.0.

Any other information on results incl. tables

No skin reactions were observed in any of the 20 test animals, neither at the 24 h nor at the 48 h reading.

 

Shortly after removal of the challenge patch, slight redness (score 1) was observed in 8 of 20 animals of the test group. This effect was not seen any more at the 24 h reading. Control animal did not show any skin reaction after challenge.

 

Following intradermal injection (induction), all animals of the test group as well as of the control group showed the same response.

 

Local skin reactions after intradermal injection (induction treatment)

 

	Test group	Controls
0.1 mL FCA (emulsion)	red area (grade 2)	red area (grade 2)
0.1 mL TS in vehicle / vehicle only	slight redness (grade 1)	slight redness (grade 1)
0.1 TS in FCA / vehicle in FCA	red area (grade 2)	red area (grade 2)

 

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

Under the conditions of this guinea pig maximization test, the supporting substance versatic 913D (C9-C13 neo fatty acids) (substitute for 3, 5, 5-trimethylhexanoic acid) was demonstrated not to act as skin sensitiser.

Executive summary:

In a dermal sensitisation study according to OECD test guideline 406 (Skin Sensitisation), Versatic 913D was tested using the Guinea Pig Maximisation Test. 20 test animals were induced by intradermal injection with 0.1 mL of 2.0% TS in corn oil and with 0.1 mL of 2.0% TS in FCA. For the topical induction, the injection site was treated 7days after the initial injection for 48 hours with pure TS (patch application). Challenge exposure followed 14 days later. Pure TS loaded on a patch was applied for 24 hours to one flank of the test animals. Reading of the skin reaction of test and control animals was taken shortly, and 24 and 48 h after removal of the patches (ca. 24, 48, and 72 h after the start of the challenge application).

 

For induction, controls (10 animals) were treated such as the test animals but test substance was omitted from the test mixtures.

 

No skin reactions in any of the 20 test animals were observed neither at the 24 h nor at the 48 h reading of the challenge period. Under the conditions of this study, Versatic 913D is not a dermal sensitizer.

 

This dermal sensitization study is acceptable and satisfies the guideline requirements for a skin sensitisation study (OECD 406) with minor restrictions (no reliability check reported).