Registration Dossier

Administrative data

Description of key information

A number of studies are available for read-across substances.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation, other
Remarks:
QSAR
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Study period:
Not stated
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
Qualifier:
no guideline followed
Principles of method if other than guideline:
The authors developed quantitative structure-toxicity relationship (QSTR) models for assessing dermal sensitization using guinea pig maximization test (GPMT) results. The models are derived from 315 carefully evaluated chemicals. There are two models, one for aromatics (excluding one-benzene-ring compounds), and the other for aliphatics and one-benzene-ring compounds. For sensitizers, the models can resolve whether they are weak/moderate or severe sensitizers. The statistical methodology, based on linear discriminant analysis, incorporates an optimum prediction space (OPS) algorithm. This algorithm ensures that the QSTR model will be used only to make predictions on query structures which fall within its domain. Calculation of the similarities between a query structure and the database compounds from which the applicable model was developed are used to validate each skin sensitization assessment, the cross-validated specificity of the equations ranges between 81 and 91%, and the sensitivity between 85 and 95%. For an independent test set, specificity is 79%, and sensitivity 82%.
GLP compliance:
not specified
Species:
other: QSAR modelling
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
The QSAR results are compared with data from guinea pig studies entered into TOPKAT - no further details available
Positive control results:
Not applicable
Reading:
other: QSAR evaluation
Group:
other: QSAR
Remarks on result:
other: Reading: other: QSAR evaluation. Group: other: QSAR.

Ethylhexyl palmitate was identified as a non-sensitiser.

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Ethylhexyl palmitate was identified as a non-sensitiser in literature and this evaluation was confirmed by the QSAR model described in this paper
Executive summary:

The salient differences of this QSTR model for skin sensitization based on the GPMT assay compared with prior publications include: (1) a considerably larger training set, and thus broader application domain encompassing wider chemical diversity.

(2) that the model resolves the strength of sensitization into weak/moderate and strong categories

(3) that the use of OPS ensures that only query compounds that fit within the model's domain will be assessed, thus avoiding the production and distribution of invalid results--this capability does not, and cannot, exist in expert systems such as DEREK.

The limitations of this QSTR model are basically:

(I) that the GPMT, due to its very nature, tends to overpredict sensitization compared with assays in humans,

(2) that the training set, extensive though it may be, does not encompass as many compounds and as much chemical diversity as one might wish --the release of proprietary data by manufacturers would greatly remediate this problem; and

(3) no account has been taken of previously identified modes of a c t i o n - - b e t t e r models would probably result if submodels were limited to compounds with a single mode of action

Despite these relative pros and cons, the QSAR model did predict the nonsensitising nature of Ethylhexyl palmitate, as indicated in prior literature.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1963
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Very little information provided on the materials and methods of the study. Read across to a study result from an investigation using a similar material is justified for members of the Epoxidised Oils and Derivatives group. Four epoxidised oils and esters (linseed, soybean,9-octadecanoate propylene glycol ester and 2-ethylhexyl tallate ester ETP). The C14-C22, 2-ethylhexylesters are listed as similar products on the market to ETP based on fatty acids from other naturally occurring fatty acids This group of epoxies are identified as sharing common structural and functional similarities, recognised in an OECD SIDS review as a single category, and therefore justifying read-across between data for different members of the group. Consequently data sharing between ESBO epoxidised soybean oil, ELO epoxidised Linseed oil and ETP epoxidised 2ethylhexyl tallate and fatty acids, C14-C22, 2-ethylhexylesters, epoxidised is commonly utilised in the preparation of this dossier. Read-across bridges are used for members of the EOD group where appropriate, is justified based on similar toxicity profiles and structural and functional similarities.
Qualifier:
no guideline followed
Principles of method if other than guideline:
No details of the method stated other than indicating the technique involved 8 intracutaneous injections of 0.1 mL of test material to guinea pigs (3/week on alternate days), followed by a 3 week incubation period then a challenge dose with examinations 24 and 48 hours after challenge. The design was probably similar to Maurer's intracutaneous method.
GLP compliance:
no
Type of study:
intracutaneous test
Justification for non-LLNA method:
Study performed prior to validation and adoption of the LLNA.
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No data
Route:
intradermal
Vehicle:
no data
Concentration / amount:
0.1 mL of the diluted epoxy materials
Route:
intradermal
Vehicle:
no data
Concentration / amount:
0.1 mL of the diluted epoxy materials
No. of animals per dose:
Test group of twenty guinea pigs
Details on study design:
Sensitisation of guinea pigs was determined by a technique consisting of eight intracutaneous injections (three per week on alternate days) of 0.1 mL of the diluted epoxy material. A three week incubation period was followed by a challenge dose, and examinations for possible sensitisation reactions were made 24 and 48 hours thereafter.
Challenge controls:
No data provided
Positive control substance(s):
not specified
Positive control results:
No data
Reading:
other: 24 and 48 hours post challenge
Hours after challenge:
24
Group:
test group
Dose level:
dose not stated in publication
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: other: 24 and 48 hours post challenge. . Hours after challenge: 24.0. Group: test group. Dose level: dose not stated in publication. No with. + reactions: 0.0. Total no. in groups: 20.0.

No further information on results

Interpretation of results:
GHS criteria not met
Conclusions:
It was concluded that the test material was not sensitising.
Executive summary:

Sensitisation of guinea pigs was determined by a technique consisting of eight intracutaneous injections (three per week on alternate days) of 0.1 mL of the diluted epoxy materials. A three week incubation period was followed by a challenge dose, and examinations for possible sensitisation reactions were made 24 and 48 hours thereafter.

It was concluded that the test material was not sensitising. According to Directive 67/548/EEC, no classification is warranted. According to Regulation (EC) No. 1272/2008, no classification is warranted.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1977
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
A limited synopsis of the data, generated prior to adoption of GLP or standard regulatory guidelines, is available for a human repeat insult patch test for a similar material - ethylhexyl palmitate. For all of these reasons the relevance of the information to the skin irritancy of fatty acids, C12-20 and C12-20 unsaturated, 2-ethylhexyl esters is not assignable.
Qualifier:
no guideline followed
Principles of method if other than guideline:
25 healthy human volunteers wee exposed to five 48 hour periods of induction exposure followed by a ten day rest period and then challenge application by 48hour occluded topical exposure. Reactions were observed and assessed immediately and 24 hours after challenge patch removal

The method was outlined as the Maximisation test by Professor Klignman in J.I.D. Vol 47: No 5: 393-409 "Updataing the Maximisation Test for Identifying Contact Allergens" - Contact Dermatitis, 1975; 1:231-239
GLP compliance:
no
Type of study:
patch test
Justification for non-LLNA method:
Study performed prior to validation and adoption of the LLNA.
Species:
human
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
25 healthy human volunteers - adult males (12) and females (13) in the age range 18-30 years, all but five were Caucasian.

No information given relating to environmental conditions but assumed to be normal home environments except on dosing days
Route:
epicutaneous, occlusive
Vehicle:
no data
Concentration / amount:
No information supplied in report synopsis related to test material concentrations. It is likely the material was applied undiluted since preliminary investigations revealed no signs of irritation and the sites were pre-treated with SLS, this is unnecesssary if there was a possibility pf applying a greater concentration of test material in vehicle.
Route:
epicutaneous, occlusive
Vehicle:
no data
Concentration / amount:
No information supplied in report synopsis related to test material concentrations. It is likely the material was applied undiluted since preliminary investigations revealed no signs of irritation and the sites were pre-treated with SLS, this is unnecesssary if there was a possibility pf applying a greater concentration of test material in vehicle.
No. of animals per dose:
One group of 25 volunteers
Details on study design:
RANGE FINDING TESTS: a single volunteer was tested for possibe irritation following topical application tothe forearm - no irritation was evident

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 5
- Exposure period: 48 hrs
- Test groups: one test group
- Control group: no details
- Site: forearm or dorsum

B. CHALLENGE EXPOSURE
- No. of exposures: single exposure
- Day(s) of challenge: not stated - challenge was 10 days after last induction application
- Exposure period: 48 hrs
- Concentrations: not specified - assumed to be undiluted ethylhexyl palmitate
- Evaluation (hr after challenge): immediately and 24 hours
Challenge controls:
Not applicable
Positive control substance(s):
not specified
Positive control results:
No information
Reading:
1st reading
Group:
test group
Dose level:
not specified
No. with + reactions:
0
Total no. in group:
25
Clinical observations:
no signs recorded
Remarks on result:
other: Reading: 1st reading. Group: test group. Dose level: not specified. No with. + reactions: 0.0. Total no. in groups: 25.0. Clinical observations: no signs recorded.
Reading:
2nd reading
Hours after challenge:
24
Group:
test group
Dose level:
not specified
No. with + reactions:
0
Total no. in group:
25
Clinical observations:
None rcorded
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 24.0. Group: test group. Dose level: not specified. No with. + reactions: 0.0. Total no. in groups: 25.0. Clinical observations: None rcorded.
Interpretation of results:
not sensitising
Conclusions:
In this human repeat insult patch test, ethyl hexylpalmitate was applied to 25 healthy adult volunteers on five occasions during induction and then 10 days later a topical challenge dose was applied. No signs of sensitisation or irritation were observed.
Executive summary:

In this human repeat insult patch test, ethyl hexylpalmitate was applied to 25 healthy adult volunteers on five occasions during induction and then 10 days later a topical challenge dose was applied. No signs of sensitisation or irritation were observed.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
Not stated
Reliability:
2 (reliable with restrictions)
Qualifier:
no guideline followed
Principles of method if other than guideline:
Human repeat insult patch test according to Kligman design
GLP compliance:
no
Type of study:
patch test
Justification for non-LLNA method:
Study performed prior to validation and adoption of the LLNA.
Species:
human
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No data
Route:
other: human patch test - no further details
Vehicle:
petrolatum
Concentration / amount:
4% challenge concentration. The induction concentration is not specified
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
4% challenge concentration. The induction concentration is not specified
No. of animals per dose:
25 human volunteers
Details on study design:
Human repeat insult patch test - no further details provided
Challenge controls:
No
Positive control substance(s):
not specified
Positive control results:
No information
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
4% in petrolatum
No. with + reactions:
0
Total no. in group:
25
Clinical observations:
No indications of sensitisation
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 4% in petrolatum. No with. + reactions: 0.0. Total no. in groups: 25.0. Clinical observations: No indications of sensitisation.
Interpretation of results:
not sensitising
Conclusions:
A human patch test in 25 volunteers resulted in no indications of sensitisation when challenged with 4% ethylhexyl palmitate.
Executive summary:

A maximization test was carried out on 25 volunteers. The material (RIFM no. 77-478) was tested at a concentration of 4% in petrolatum and produced no sensitization reactions. A human patch test in 25 volunteers resulted in no indications of sensitisation when challenged with 4% ethylhexyl palmitate.

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

Several investigations included analogous materials or other UVCBs in an assessment of sensitising potential. Ethyl hexyl palmitate was investigated by Kligman, in a human repeat insult patch test, no signs of sensitisation or irritation were observed. Weil investigated the sensitising potential of ESBO in an open epicutaneous assay - no signs of sensitisation were evident. Ethyl hexyl palmitate was investigated as part of a review of fragrance additives. A 4% solution applied at challenge in ahuman repeat insult patch test resulted in no evidence ofsensitisation. As part of QSAR modeling validation, ethylhexyl palmitate was also identified as non-sensitising.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Sensitisation studies performed with read-across substances show that fatty acids C12 -20 and C12 -20 unsaturated, 2 -ethylhexyl esters do not require classification as potential skin sensitisers under the CLP Regulation.