Registration Dossier

Administrative data

Description of key information

Skin irritation (OECD 404): not irritating
Eye irritation (OECD 405): not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
June 6th, 1989 - June 23rd, 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions Limited details on test substance
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Limited details on test substance
GLP compliance:
yes
Species:
rabbit
Strain:
other: Kleinrusse, Chbb:HM
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Fa. Thomae, Bieberach, Germany
- Weight at study initiation: mean: 2420 g
- Diet: Altromin 2023, ad libitum
- Water: ad libitum
- Acclimatisation: approx. 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 45-70
- Photoperiod (hrs dark / hrs light):12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
Duration of treatment / exposure:
4 h
Observation period:
72 h
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm²

SCORING SYSTEM: according to 84/449/EWG [Amtsblatt der Europäischen Gemeinschaft L 251/108]
Irritation parameter:
erythema score
Basis:
animal: #1176
Time point:
other: 24 h, 48 h and 72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Basis:
animal: #1177
Time point:
other: 24 h, 48 h and 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
erythema score
Basis:
animal: #1179
Time point:
other: 24 h, 48 h and 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
edema score
Basis:
mean
Remarks:
of all three animals
Time point:
other: 24 h, 48 h and 72 h
Score:
0
Max. score:
4
Reversibility:
other: No effects observed

Erythema score

Animal Number

1 h

1 day

2 days

3 days

1176

0

1

1

0

1177

0

1

0

0

1179

0

1

0

0

 

Oedema Score

Animal Number

1 h

1 day

2 days

3 days

1176

0

0

0

0

1177

0

0

0

0

1179

0

0

0

0

 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
July 10th, 1989 - July 13th, 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions. Limited details on study substance
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Limited details on study substance
GLP compliance:
yes
Species:
rabbit
Strain:
other: Kleinrusse, Chbb
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Thomae, Biberach, Deutschland
- Age at study initiation: 6 months
- Weight at study initiation: 2550 g
- Diet: Altromin 2023 ad libitum
- Water:ad libitum
- Acclimation period: 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 45-70
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml (slightly warmed)
Duration of treatment / exposure:
24 h
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, rinsed with water
- Time after start of exposure: 24 h


SCORING SYSTEM: According to 84/449/EWG


TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of all three animals
Time point:
other: 24 h, 48 h and 72 h
Score:
0
Max. score:
4
Reversibility:
other: No effect
Irritation parameter:
iris score
Basis:
mean
Remarks:
of all three animals
Time point:
other: 24 h, 48 h and 72 h
Score:
0
Max. score:
2
Reversibility:
not specified
Remarks:
No effect
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of all three animals
Time point:
other: 2 h4, 48 h and 72 h
Score:
0
Max. score:
3
Reversibility:
other: No effect
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of all three animals
Time point:
other: 24 h, 48 h and 72 h
Score:
0
Max. score:
4
Reversibility:
other: No effect

 

Animal

Hours after application

1

24

48

72

A

B

C

D

E

A

B

C

D

E

A

B

C

D

E

A

B

C

D

E

1192

0

0

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1193

0

0

1

0

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1195

0

0

1

0

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

A = Corneal Score

B = Iris Score

C = Erythema Score

D = Chemosis Score

E = Exsudation Score

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for grouping of substances and read-across

There are not sufficient data available for the skin and eye irritating properties of Fatty acids, C14-18 and C16-18-unsatd., mixed esters with castor oil, castor oil fatty acids, 2-ethylhexanoic acid and 2,2-bis(hydroxymethyl)-1-butanol (CAS 92113-48-9). In order to fulfil the standard information requirements set out in Annex VIII, 8.1.1 and 8.2.1, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from a structurally related substance was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, 1.5, of Regulation (EC) No 1907/2006, whereby physicochemical, toxicological and ecotoxicological properties may be predicted from data for reference substance(s) by interpolation to other substances on the basis of structural similarity, Fatty acids, C16-18, triesters with trimethylolpropane (CAS 91050-90-7) is selected as source substance for assessment of in vivo skin and eye irritation.

Irritation/Corrosion

CAS

92113-48-9 (a)

91050-90-7 (b)

Chemical name

Fatty acids, C14-18 and C16-18-unsatd., mixed esters with castor oil, castor oil fatty acids, 2-ethylhexanoic acid and 2,2-bis(hydroxymethyl)-1-butanol

Fatty acids, C16-18, triesters with trimethylolpropane

MW

512.8 – 975.5

849.40 - 933.56 g/mol

Skin corrosion (in vitro)

Experimental result:
not corrosive

--

Skin irritation (in vivo)

RA: CAS 91050-90-7

Experimental result:
not irritating

Eye corrosion (in vitro)

Experimental result:
not corrosive/severely irritating

--

Eye irritation (in vivo)

RA: CAS 91050-90-7

Experimental result:
not irritating

(a) The substance subject to the REACh Phase-in registration deadline of 31 May 2013 is indicated in bold font. Only for this substance a full set of experimental results and/or read-across is given.

(b) Reference (read-across) substances are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

The above mentioned substances are considered to be similar on the basis of the similarities in structure, properties and/or activities. The available endpoint information is used to predict the same endpoint for Fatty acids, C14-18 and C16-18-unsatd., mixed esters with castor oil, castor oil fatty acids, 2-ethylhexanoic acid and 2,2-bis(hydroxymethyl)-1-butanol (CAS 92113-48-9).

A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Discussion

Skin irritation/corrosion

An in vitro skin corrosion study was performed with the target substance according to OECD 431 and in compliance with GLP (Wingenroth, 2012). 50 µl of the test substance were applied to a three-dimensional reconstructed human epidermis model (EST-1000) for 3 and 60 min under open conditions. After the treatment, the cell viability was measured by means of the MTT reduction assay. Relative cell viabilities of 99.9% and 103.7% were observed for the 3 and 60 min treatments, respectively. Classification was done in accordance with the existing guideline and internationally accepted protocols, i.e. viability after 3 min and/or less than 15% viability after a 60 min incubation period. The test item was characterised by no significant impact on cell viability after 3 min or after the 60 min period. In conclusion, Fatty acids, C14-18 and C16-18-unsatd., mixed esters with castor oil, castor oil fatty acids, 2-ethylhexanoic acid and 2,2-bis(hydroxymethyl)-1-butanol is not corrosive.

For assessment of the irritating potential, the results from an OECD 404 GLP-study with the analogue substance Fatty acids, C16-18, triesters with trimethylolpropane were used for read-across (Steiling, 1989). Semi-occlusive treatment for 4 h resulted in slight erythema in all 3 rabbits after 24 h; in one case (animal 1), erythema remained up to 48 h. The finding was fully reversible for all 3 animals within 72 h. No edema was seen in any animal throughout the whole study. The mean erythema scores over 24, 48, and 72 h for each animal were 0.7, 0.3, and 0.3, respectively. Thus, Fatty acids, C16-18, triesters with trimethylolpropane is considered to be not skin irritating.

 

Eye irritation/corrosion

An in vitro eye corrosion study was performed with the target substance according to OECD 437 (BCOP) and in compliance with GLP (Stelter, 2012). 750 µl of the test substance were applied to three eyes from cattle for 10 min. Afterwards the substance was removed and the epithelium was washed at least three times. The corneal opacity was determined via an opacitometer. For the determination of the corneal permeability sodium fluorescein solution was added to the anterior chamber of the cornea holder while the posterior chamber was filled with fresh medium. The amount of sodium fluorescein that crosses into the posterior chamber was quantitatively measured via UV/VIS spectrophotometry at 490 nm recorded as optical density (OD490). Based on the results of the opacity and permeability measurements, the in-vitro irritancy score (IVIS) was calculated. The IVIS value was 20.83 for the test substance. For a positive result the IVIS is = 55.1. In conclusion, Fatty acids, C14-18 and C16-18-unsatd., mixed esters with castor oil, castor oil fatty acids, 2-ethylhexanoic acid and 2,2-bis(hydroxymethyl)-1-butanol is not a severe eye irritant or corrosive to the eye.

For assessment of the irritating potential, the results from an OECD 405 GLP-study with the analogue substance Fatty acids, C16-18, triesters with trimethylolpropane were used for read-across (Steiling, 1989). Three rabbits were treated with 0.1 mL of the test substance. After 24 h the eyes were rinsed with water. The eyes were scored at 1, 24, 48, and 72 h. Redness of the conjuctivae of grade 1 was seen in all 3 animals at reading time point 1 h. In 2 cases this was accompanied by exudation. These effects disappeared within 24 h. The mean scores for cornea, iris, conjunctivae, and chemosis over 24, 48, and 72 were 0. Thus, Fatty acids, C16-18, triesters with trimethylolpropane has no eye irritating properties.

Conclusion

Fatty acids, C14-18 and C16-18-unsatd., mixed esters with castor oil, castor oil fatty acids, 2-ethylhexanoic acid and 2,2-bis(hydroxymethyl)-1-butanol was not corrosive to the skin and to the eye in vitro. In addition, the analogue substance Fatty acids, C16-18, triesters with trimethylolpropane is not irritating to the skin and eyes in vivo. In conclusion, based on experimental results and data from an analogue substance, Fatty acids, C14-18 and C16-18-unsatd., mixed esters with castor oil, castor oil fatty acids, 2-ethylhexanoic acid and 2,2-bis(hydroxymethyl)-1-butanol is considerd to be not irritating to skin and eyes.


Justification for selection of skin irritation / corrosion endpoint:
The selected study is the most adequate and reliable study based on overall quality assessment (refer to the endpoint discussion for further details).
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details).

Justification for selection of eye irritation endpoint:
The selected study is the most adequate and reliable study based on overall quality assessment (refer to the endpoint discussion for further details).
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details).

Justification for classification or non-classification

Based on substance specific studies and read-across following an analogue approach, the available data on the skin and eye irritation potential do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

There are no data available on respiratory irritation.