Registration Dossier

Administrative data

Description of key information

Skin and eye irritation tests were available for two read-across substances - epoxidised soybean oil and octyl stearate. Read-across to both analogues is justified and in each case the test results indicate low ocular irritancy and low or slight skin irritation.  The human patch test for ethyl hexyl palmitate sensitisation potential also indicated no evident irritation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint:
skin irritation / corrosion
Remarks:
other: human repeat insult patch test
Type of information:
experimental study
Adequacy of study:
supporting study
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 persiods of induction exposure folloed 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
Species:
human
Strain:
not specified
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
Type of coverage:
occlusive
Preparation of test site:
other: pretreated by application of 2.5% aqueous sodium lauryl sulphate
Vehicle:
not specified
Controls:
no
Amount / concentration applied:
No details available for dose of test material applied in induction or challenge phases
Duration of treatment / exposure:
Five 48-hour periods of occluded exposure by topical application to forearm or dorsum, followed by 10 day rest period and then a 48 hour exposure under occlusive dressing to a naive site.
Observation period:
immediately and 24 hours after challenge dressing removal
Number of animals:
25 human volunteers
Details on study design:
TEST SITE
- Area of exposure: Not specified in study synopsis
- % coverage: Not stated
- Type of wrap if used: occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not stated

SCORING SYSTEM: Not stated but method details indicate a modified Draize assessment

The reactions for all 25 volunteers immediately and 24 hours after challenge were scored as "0" for irritation/sensitisation

Interpretation of results:
study cannot be used for classification
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 irritation / corrosion
Remarks:
other: various investigations are reported by various methods for a range of stearates
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Peer-reviewed review of several safety assessments
Justification for type of information:
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, justified based on similar toxicity profiles and structural and functional similarities.
Qualifier:
no guideline required
Principles of method if other than guideline:
Octyl stearate was tested for irritation potential in three rabbit irritation tests - two assays as detailed in the Journal Officiel de la Republique Francaise and one test according to the methods detailed in the Federal Hazardous Substances Act, 16 CFR 1500.3 and 16 CFR 1500.41. In two assays the undiluted octyl stearate was applied to the intact skin of six New Zealand White rabbits for 24 hours. In the second test following the same regimen, a 10% aqueous solution was applied.

In the third assay 0.5 mL was applied to test sites on six rabbits each with intact and abraded test areas.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No details provided

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No details of environmental conditions provided in publication

IN-LIFE DATES: From: To: Not stated in publication
Type of coverage:
occlusive
Preparation of test site:
other: intact and abraded sites used on skin clipped free of hair
Vehicle:
water
Controls:
no
Amount / concentration applied:
Undiluted octyl stearate applied in first test and a 10% aqueous solution in the second assay. 0.5 ml applied to each test site.

In the third test 0.5 mL undiluted octyl stearate was applied to intact and abraded skin sites
Duration of treatment / exposure:
24 hour exposure under occlusive dressing
Observation period:
Assessed for up to 72 hours after dosing
Number of animals:
6 albino rabbits per test
Details on study design:
TEST SITE
- Area of exposure: No details available
- % coverage: Not stated
- Type of wrap if used: Occlusive dressing but no further specific details

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No indication in report of testsubstance removal by washing
- Time after start of exposure: Not applicable

SCORING SYSTEM: Draize . PII values derived
Interpretation of results:
GHS criteria not met
Conclusions:
In one of three assays a low level of iriation response was observed but the test included reactions from abraded sites in the overall assessment of octyl stearate. No classification is required under the CLP Regulation. It is appropriate to read across to octyl stearate to determine classification requirements for fatty acids, C12-20 and C12-20 unsaturated, 2-ehylhexyl esters
Executive summary:

Octyl stearate was tested for irritation potential in three rabbit irritation tests - two assays as detailed in the Journal Officiel de la Republique Francaise and one test according to the methods detailed in the Federal Hazardous Substances Act, 16 CFR 1500.3 and 16 CFR 1500.41. In two assays the undiluted octyl stearate was applied to the intact skin of six New Zealand White rabbits for 24 hours. In the second test following the same regimen, a 10% aqueous solution was applied. In the third assay o.5 mL was applied to test sites on six rabbits each with intact and abraded test areas.

In one of three assays a low level of iriation response was observed but the test included reactions from abraded sites in the overall assessment of octyl stearate. No classification is required under Regulation 1272/2007. Itis appropriate to read across to octyl stearate to determine classification requirements for fatty acids, C12-20 and C12-20 unsaturated, 2-ehylhexyl esters

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
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 information provided to determine methods used to assess ocular irritation - the results indicate that only corneal injury was assessed and other parameters normally included in current guidelines (e.g. iris and conjunctival responses) were not assessed.
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
No data supplied
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
No details are provided to determine how rabbit ocular injury was assessed. No methodological information was available.
Duration of treatment / exposure:
No details for duration of exposure
Observation period (in vivo):
No data
Number of animals or in vitro replicates:
No data
Details on study design:
No details supplied in report publication
Irritation parameter:
cornea opacity score
Basis:
other: the basis for the ocular score is not stated in publication
Time point:
other: No details provided
Score:
1
Reversibility:
not specified
Remarks on result:
other: The value for ocular injury cannot be interpreted since no details are provided for its derivation
Irritant / corrosive response data:
Corneal injury score of 1 recorded
Interpretation of results:
study cannot be used for classification
Conclusions:
The indication is that some degree of corneal injury was induced by instillation of soybean oil, epoxidised. However, the 60 comparative materials listed in this report had scores in the range of 0-10 indicating the corneal injury induced by ESBO is slight or minimal.
Executive summary:

Carcinogenic and acute toxicity potential of the test material was assayed.

Irritation

The irritation result given is provided for irritation on an uncovered rabbit belly and was given a score of 2.

Toxicity

A wide range of toxicity and irritation of epoxy monomers is documented in this report. No consistent correlations with structure are evident.

Carcinogenicity

The test was successfully completed. The test material was not considered to be tumorigenic to the mouse skin.

Sebaceous Gland Suppression

The mena number of sebaceous glands per square centimeter of skin of epoxide-dosed mice has been graded against that of the control mice. As the material was applied undiluted, it was compared to a distilled water control group. This substance was tested by both the sebaceous gland (S.G.T.) and the lifetime tests (L.T.T.). The L.T.T. was negative, the tumour and the cancer index were both 0.0. It was given a S.G.T. grade of 0.

The authors of this report have indicated that the S.G.T., based on the data in this report, is merely a crude screen to indicate potential L.T.T. tumorigens, not a test to be used to from definite positive or negative conclusions concerning tumorigenesis.

Sensitisation:

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.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Peer-reviewed review of several safety assessments
Qualifier:
according to
Guideline:
other: Methods outlined in Journal Officiel de la Republique Francais
Principles of method if other than guideline:
Six rabbits exposed on single occasion to undiluted test material instilled into one eye at a volume of 0.1 mL. The eyes were not rinsed. Ocular assessments were completed at 1 hour and 1,2,3,4 and 7 days after dosing.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
No details provided in synopsis
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
Exposure was unlimited - the eyes were not rinsed. The observation period was 7 days.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
6
Details on study design:
The test material was instilled into one eye of each of six rabbits, the contralateral eye serving as an inherent control. O.1 mL of undiuted material was placed in to the conjuctival sac, the eyes were not rinsed and were assessed for reactions after one hour and then 1, 2, 3, 4, and 7 days after dosing.
The assessment system was based on a scale of ocular reaction graded from 0-100 (Kay & Calandra). An ocular index of less than 10 using this scale indicates no irritation.
Irritation parameter:
overall irritation score
Remarks:
4.67, 0.0, 0.0, 0.0, 0.0 and 0.0
Basis:
mean
Time point:
other: 1h and 1, 2, 3, 4 and 7 days after dosing
Score:
4.67
Max. score:
100
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: octyl stearate was not irritating to rabbit eyes in a standard ocular itrritation assessment
Irritant / corrosive response data:
Slight transient eye irritation observed within an hour of instillation had resolved within 24 hours. The mean scores for six rabbits over the 24-72 h assessment was zero. No classification for ocular irritancy is indicated
Other effects:
None reported

No other information

Interpretation of results:
GHS criteria not met
Conclusions:
Slight transient eye irritation observed within an hour of instillation had resolved within 24 hours. The mean scores for six rabbits over the 24-72 h assessment was zero. No classification for ocular irritancy is indicated under the CLP Regulation.
Executive summary:

The test material was instilled into one eye of each of six rabbits, the contralateral eye serving as an inherent control. O.1 mL of undiuted material was placed in to the conjuctival sac, the eyes were not rinsed and were assessed for reactions after one hour and then 1, 2, 3, 4, and 7 days after dosing. The assessment system was based on a scale of ocular reaction graded from 0-100 (Kay & Calandra). An ocular index of less than 10 using this scale indicates no irritation. Slight transient eye irritation observed within an hour of instillation had resolved within 24 hours. The mean scores for six rabbits over the 24-72 h assessment was zero. No classification for ocular irritancy is indicated.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In vivo skin irritation was investigated as part of a human patch test for determining sensitisation potential of ethylheyl palmitate - no signs of irritation were observed. Dermal irritation was investigated at intact and abraded sites on rabbits using octyl stearate - in three assays using undiluted octyl stearate or a 10% dilution there were limited signs of irritation. The highest PII obtained was 1.42 - interpreted as non-irritatiing.

An in vivo assessment of corneal change following application of ESBO resulted in no indications of corneal damage.

In a second in vivo study, octyl stearate was instilled undiluted in to the eyes of six rabbits and elicited transient slight irritation that resolved with in 24 hours. The mean score for the period of interest (24 -72 h) was 0.0 and the material was non-irritating to rabbit eyes.

Justification for classification or non-classification

None of the available study results indicate that CLP classification thresholds for skin or eye irritancy are exceeded. Fatty acids C12 -20 and C12 -20 unsaturated, 2 -ethylhexyl esters is not classified for skin irritation or eye irritation based on read-across to various similar substances.