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Administrative data

Description of key information

Studies on skin sensitisation (animal and human skin sensitisation tests) are available for the following fatty acid category members:
CAS# 124-07-2, C8 (Opdyke, 1981)
CAS# 123-99-9, C9 (Lea, 1995)
CAS# 334-48-5, C10 (Sauter and Ritz, 1975)
CAS# 143-07-7, C12 (Gloxhuber and Potokar, 1979)
All available skin sensitisation studies showed that fatty acids are not skin sensitising.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given
Principles of method if other than guideline:
The experiment was conducted according to the method of B. Magnusson and M. Kligman [The Journal of Investigative Dermatology, Volume 52, No. 3 and Allergic Contact Dermatitis in the Guinea Pig., Charles C. Thomas Publisher, Springfield, Illinois, 1970, USA].
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The test was done before LLNA as first-choice method for in vivo testing was set into force.
Species:
guinea pig
Strain:
other: Pirbright-white
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: mean 374 g (test group), 389 g (control group)
Route:
intradermal
Vehicle:
other: ethanol
Concentration / amount:
Challenge: 2.5%
Route:
epicutaneous, occlusive
Vehicle:
other: ethanol
Concentration / amount:
Challenge: 2.5%
No. of animals per dose:
20
Details on study design:
CHALLENGE EXPOSURE
- Exposure period: 24 hours
- Test groups: 20 animals
- Control group: 10 animals
- Concentrations: 2.5%
- Evaluation (hr after patch removal): 24 and 48 hours

Challenge controls:
10 animals
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
2.5%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no effects
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 2.5%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no effects.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
2.5%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no effects
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 2.5%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no effects.
Group:
positive control
Remarks on result:
not measured/tested
Group:
negative control
Remarks on result:
not measured/tested

All test animals and controls showed no skin effects (0%). Lauric acid is not sensitizing in guinea pigs.

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
Conclusions:
CLP: not classified
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
26 Apr - 25 May 1995
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The test was done before LLNA as first-choice method for in vivo testing was set into force.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Olac
- Weight at study initiation: 318 - 347 g
- Acclimation period: 4 days

Animal room environmental measurements showed, the temperature and humidity were maintained between the specified limits for the duration of the study.
Route:
intradermal and epicutaneous
Vehicle:
other: Acetone/PEG400
Concentration / amount:
Induction application: 0.25 % (intradermal) and 50.0 % (epicutanous)
Challenge application: 50.0 % (epicutanous)
Route:
epicutaneous, occlusive
Vehicle:
other: Acetone/PEG400
Concentration / amount:
Induction application: 0.25 % (intradermal) and 50.0 % (epicutanous)
Challenge application: 50.0 % (epicutanous)
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS:
Intradermal injection: Preliminary irritation studies were carried out to determine concentrations of test material suitable for sensitization challenge: Four male guinea pigs weighing between 348-374 g at the start of the study were injected intradermally on the clipped flanks with 0.1 mL aliquots of 2.0, 1.0, 0.5, 0.25, 0.1, 0.05 % (w/v) test material in corn oil. Approximately 24 hours later the reactions were examined for size in millimetres (length and breath), erythema and oedema.
Occluded patch: Four male guinea pigs weighing between 501-514 g were selected. For each guinea pig three eight millimetre diameter filter paper patches were saturated with the following concentrations: 1.0, 5.0, 10.0 % (w/v) of test material in acetone/PEG400 and applied to the shaved and clipped flanks. The patches were left on for 24 hours and assessments carried out approximately 24 and 48 hours after the patches were removed. The study was repeated using an additional four male guinea pigs weighing between 501-608 g to find a suitably irritant concentration for induction application.

MAIN STUDY
Ten guinea pigs (five male and five female) weighing between 318-347 g were randomly selected for the test group and five guinea pigs (males) were selected to be weight matched controls for challenge. All guinea pigs were examined daily and weighed weekly as an indication of general health.

A. INDUCTION EXPOSURE
- No. of exposures: 2
On day 1, at the intradermal induction test animals were treated with 0.25 % test material. Eight days later, the test and control animals were treated with 10.0 % (w/w) sodium dodecyl sulphate in petrolatum by open application over the induction injection sites. Twenty four hours later the test animals were treated with 50.0 % test material by induction application.


B. CHALLENGE EXPOSURE
- No. of exposures: 1
Eleven days after the induction application the test animals and control animals were challenged with 50.0% test material by occluded patch.
Challenge controls:
5 males
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no effects.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no effects.
Group:
positive control
Remarks on result:
not measured/tested
Group:
negative control
Remarks on result:
not measured/tested

There was no evidence of toxicity of the test substance. Daily examination showed all guinea pigs to be in good health and no significant differences in body weights were observed between the test and control guinea pigs.

As a result of the preliminary irritation tests 0.25 % was selected from the preliminary irritation test to be the highest suitably irritant concentration for the intradermal injection induction. It was not possible to establish a sufficiently irritant concentration of the test material for induction application from the preliminary work, therefore the animals were treated on day 8 of the study with 10.0 % sodium dodecyl sulphate in petrolatum by open application over the induction injection sites, followed twenty four hours later by an induction application patch of 50.0 %. 50.0 % was selected as it was the highest non-irritant concentration for the challenge patch.

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
Conclusions:
There was no evidence of sensitization reactions in any of the ten test guinea pigs challenged with 50.0 % azelaic acid at challenge. The control animals showed no response to the test material. Under the conditions of this study azelaic acid is a non sensitizer.
CLP: not classified
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given
Principles of method if other than guideline:
Buehler-Test with 20 animals which were induced by three 6 h applications within three weeks. Two weeks later the challenge application was done.
GLP compliance:
no
Type of study:
Buehler test
Justification for non-LLNA method:
The test was done before LLNA as first-choice method for in vivo testing was set into force.
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Route:
epicutaneous, occlusive
Vehicle:
other: 40% ethanol for induction; acetone for challenge
Concentration / amount:
Induction: 5%
Challenge: 5%
Route:
epicutaneous, occlusive
Vehicle:
other: 40% ethanol for induction; acetone for challenge
Concentration / amount:
Induction: 5%
Challenge: 5%
No. of animals per dose:
Test group: 20
Control group: 10
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: once a week for three weeks
- Exposure period: 6 hours
- Test groups: 20 animals
- Control group: 10 animals
- Concentrations: 5%


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: two weeks after last induction
- Exposure period: 6 h
- Test groups: 20 animals
- Control group: 10 animals
- Concentrations: 5%
- Evaluation (hr after challenge): 24 and 48 hours after application
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
an occasional very slight degree of irritation was seen
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: an occasional very slight degree of irritation was seen.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
an occasional very slight degree of irritation was seen
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: an occasional very slight degree of irritation was seen.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
an occasional very slight degree of irritation was seen
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: an occasional very slight degree of irritation was seen.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
an occasional very slight degree of irritation was seen
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: an occasional very slight degree of irritation was seen.
Group:
positive control
Remarks on result:
not measured/tested
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
Conclusions:
CLP: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Fatty acids are found in all living organisms fulfilling fundamental physiological functions within the body. Based on this role within the body no sensitization potential of fatty acids is expected as it could be demonstrated by human data with C8 fatty acid (octanoic acid) and by animal studies with C9 fatty acid (azelaic acid), C10 fatty acid (decanoic acid) and C12 fatty acid (lauric acid), respectively.

Octanoic was not found to be a skin sensitizer in a published study with 25 human subjects, who received an application of 0.3 g octanoic acid (CAS# 124-07-2) at 5% concentration under occlusion for induction onto the forearm 5 times for 24 hours (Opdyke, 1981). The challenge with a concentration of 1% did not result in any positive reaction when scored 72 and 96 hours later.

Azelaic acid (CAS# 123-99-9) was examined for its skin sensitization potential in a Guinea Pig Maximisation test which was conducted under GLP according to OECD guideline 406 (Lea, 1995). 10 Dunkin-Hartley guinea pigs received an intradermal injection of 0.25% azelaic acid for induction followed by the second induction 8 days later as an application of 50% azelaic acid on the same site, which had been previously treated with 10% SDS in petrolatum. The used concentrations were based on a preliminary range finding test, where the suitable concentrations for the intradermal injection and patch testing were evaluated. Eleven days after the induction application the test animals and the 5 control animals were challenged with 50% test material by occluded patch. As result, no sensitizing effects could be observed 24 and 48 hours after the challenge.

The skin sensitization potential of decanoic acid (CAS# 334-48-5) was tested in a Buhler test, where 20 guinea pigs were induced with an epicutanous application of 5% decanoic acid in 40% ethanol under occlusion for 6 hours once a week for three consecutive weeks (Sauter and Ritz, 1975). Two weeks after the last induction, the animals were challenged epicutanously under occlusion with a concentration of 5% decanoic acid in acetone for 6 hours. The readings 24 and 48 hours after removal of the patches revealed occasional very slight degree of irritation in the dose and control groups, respectively. However, no signs of a sensitization reaction were noted.

The same negative result was obtained for lauric acid (CAS# 143-07-7) tested in a study according to the method described by Magnusson and Kligman (Gloxhuber and Potokar, 1979). 20 female Pirbright-white guinea pigs received an induction by intradermal injection and were challenged with a concentration of 2.5% epicutanously under occlusion for 24 hours. The readings of the skin sites 24 and 48 hours later did not reveal any reaction so that lauric acid is regarded as not sensitizing to skin.


Migrated from Short description of key information:
Studies on skin sensitisation (animal and human skin sensitisation tests) are available for the following fatty acid category members:
CAS# 124-07-2, C8 (Opdyke, 1981)
CAS# 123-99-9, C9 (Lea, 1995)
CAS# 334-48-5, C10 (Sauter and Ritz, 1975)
CAS# 143-07-7, C12 (Gloxhuber and Potokar, 1979)
All available skin sensitisation studies showed that fatty acids are not skin sensitising.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

No data available.

Justification for classification or non-classification

According to CLP (1272/2008/EC) classification criteria for skin sensitisation, fatty acids do not fulfill the criteria for classification and thus a non-classification is warranted for this endpoint.