Registration Dossier

Administrative data

Description of key information

Skin irritation/corrosion: not irritating

Eye irritation (similar to OECD 405): not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
15 - 18 Jan 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: 6 New Zealand albino rabbits were exposed dermally under occlusive conditions to the undiluted test substance for 24 h. The test substance was applied to abraded and non-abraded skin sites. The skin was observed for erythema and edema (Draize scoring system) 1 and 48 h after removal of the test substance.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Nottingham University, School of Agriculture, Nottingham, UK
- Weight at study initiation: 2.59 - 3.35 kg (range: males and females)
- Housing: individually in suspended metal cages
- Diet: rabbit diet (John Waring (Feeds) Limited, Shardlow, Derbyshire, UK), ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Air changes (per hr): at least 20
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
occlusive
Preparation of test site:
other: clipped and abraded
Remarks:
test site on right flank of the animals
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL

Duration of treatment / exposure:
24 h
Observation period:
48 h
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: The test substance was introduced under a composite patch which consisted of a 2.5 cm square of absorbent lint B.P.C. backed by a 2.5 cm square of polythene with a final backing of a 4 cm square of lint. The patch was held in position by two lengths of sleek adhesive strapping in the form of a cross.

REMOVAL OF TEST SUBSTANCE
- Washing: Any residual test material was removed by gentle swabbing the test site with cotton wool soaked in lukewarm water.
- Time after start of exposure: 24 h

OBSERVATION TIME POINTS
1 and 48 h after removal of the patches


SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
animal: #3
Time point:
other: 1 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
erythema score
Basis:
animal: #1, #2, #4, #5 and #6
Time point:
other: 1 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 6 animals
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
other: not apllicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 1 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 6 animals
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
Intact skin:
At the 1-h reading time point, very slight erythema (score 1) was observed in 1/6 animals. The erythema had cleared completely within 48 hours after patch removal. No oedema was observed in any animal at any time reading time point.

Abraded skin:
Very slight erythema (score 1) was observed in 2/6 animals 1 h after patch removal. All evidence of irritation had disappeared 48 h after patch removal.



Table 1. Results of irritation test on intact and abraded skin sites 1h and 48 h after patch removal

Observation time

Rabbit no.

1

2

3

4

5

6

Erythema

Edema

Erythema

Edema

Erythema

Edema

Erythema

Edema

Erythema

Edema

Erythema

Edema

Intact skin

1 h

0

0

0

0

1

0

0

0

0

0

0

0

48 h

0

0

0

0

0

0

0

0

0

0

0

0

Abraded skin

1 h

0

0

1

0

1

0

0

0

0

0

0

0

48 h

0

0

0

0

0

0

0

0

0

0

0

0

Interpretation of results:
other: Study can not be used for classification
Conclusions:
The result of the in vivo skin irritation study is not conclusive with respect to non-classification or classification as a skin irritant and therefore requires further evaluation and/or data generation.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
26 -29 May 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The analytical purity of the test substance was not specified.
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: ESD (Chatillon sur Chalaronne, France)
- Weight at study initiation: 2-2.5 kg
- Housing: animals were housed individually in stainless steel cages with a wiremesh floor
- Diet: Food ref. 110-10 (U.A.R., Epinay sur Orge, France), ad libitum
- Water: filtered tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 30-80
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 26 May 1999 To: 29 May 1999
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: not required, untreated sites of the same animal served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
3 days
Reading time points: 1, 24, 48 and 72 h
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: a gauze patch covering the test site was held in place by micropore tape; the trunk of the animals was wrapped in an elastic gauze band and semiocclusive, adhesive tape. Access to the test site was restricted with a plastified aerated wrapping fixed to the trunk of the animals with velcro tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the remnants of the test substance were removed with distilled water or, if necessary, a suitable solvent
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
No skin irritation effects were observed at any time point in any animal.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
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:
experimental study
Adequacy of study:
key study
Study period:
28 - 31 Jan 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
limited documentation; no analytical purity of test substance given
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted Oct 2012
Deviations:
yes
Remarks:
limited documentation; no analytical purity of test substance given
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Nottingham University, School of Agriculture, Nottingham, UK
- Weight at study initiation: 2.00 - 2.42 kg (range: males and females)
- Housing: individually in suspended metal cages
- Diet: rabbit diet (J. Waring (Feeds) Limited, Shardlow, Derbyshire, UK), ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Air changes (per hr): at least 20
- Photoperiod (hrs dark / hrs light): 12 / 12
Vehicle:
unchanged (no vehicle)
Controls:
other: left eye remained untreated and served as control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL
Duration of treatment / exposure:
single application without washing
Observation period (in vivo):
72 h
Reading time points: 24, 48 and 72 h
Number of animals or in vitro replicates:
6
Details on study design:
SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: ophthalmoscope; Observation of corneal opacity was carried out under ultra-violet illumination preceded by the instillation of fluorescein into the eye.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #4 and #5
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal: #2, #3 and #6
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal: #2, #3, #4 and #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritant / corrosive response data:
3/6 animals showed conjunctival redness (score 1) 24 and 48 h after instillation, reversible within 72 h. 2/6 animals showed conjunctivae chemosis (score 1) 24 h after instillation of test substance, in one animal reversible within 48 h, in the second animal reversible within 72 h.

Table 1. Results of eye irritation study.

Alteration

Animal No.

Time (h)

 

24

 

48

 

72

mean 24/48/72 h

reversible within

Cornea

1

0

0

0

0

-

2

0

0

0

0

-

3

0

0

0

0

-

4

0

0

0

0

-

5

0

0

0

0

-

6

0

0

0

0

-

Iris

1

0

0

0

0

-

2

0

0

0

0

-

3

0

0

0

0

-

4

0

0

0

0

-

5

0

0

0

0

-

6

0

0

0

0

-

Conjunctivae Redness

1

0

0

0

0

-

2

1

1

0

0.67

72 h

3

1

1

0

0.67

72 h

4

0

0

0

0

-

5

0

0

0

0

-

6

1

1

0

0.67

72 h

Conjunctivae Chemosis

1

1

1

0

0.67

72 h

2

0

0

0

0

-

3

0

0

0

0

-

4

0

0

0

0

-

5

0

0

0

0

-

6

1

0

0

0.33

48 h

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Analogue justification

There are substance-specific data available on the skin and eye irritation potential of Fatty acids, C16 and C18-22 - unsatd., C16-18 and C18 unsatd. alkyl ester (CAS 90990-29-7). Additional data on the skin irritation potential of was provided using studies conducted with an analogue substance as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Skin irritation

In vivo

CAS 90990-29-7

A skin irritation study was performed with Fatty acids, C16 and C18-22 - unsatd., C16-18 and C18 unsatd. alkyl ester (CAS 90990-29-7) (Key, 1982). No current guideline was followed. 0.5 mL of the undiluted test substance was applied to the clipped or clipped and abraded skin of 6 New Zealand White rabbits and held in place by an occlusive dressing for 24 h. The severity of erythema and edema was scored 1 and 48 h after patch removal. The test material produced minimal erythema (score 1) in 1/6 rabbits at the intact test site and in 2/6 rabbits at the abraded test site, respectively, 1 h after patch removal. All skin irritation effects were reversible within 48 h after patch removal. No other skin irritation effects were observed in any animal (6/6) at any reading time point. Due to the short observation period, the results are not suitable for determining the classification or non-classification of the substance.

CAS 72576-80-8

A skin irritation study was performed with Hexadecanoic acid isooctadecyl ester (CAS 72576-80-8), according to EU Method B.4 and under GLP conditions (Key, 1999). 0.5 mL of the test substance was applied to the shaved skin of 3 New Zealand White rabbits and held in place by a semi-occlusive dressing for 4 h. The severity of erythema and edema was scored 1, 24, 48 and 72 h after patch removal. No skin irritation was observed at any time point in any animal; all erythema and edema scores were 0. The test substance is not considered to be irritating to the skin.

Human data

CAS 17671-27-1

In a single exposure patch test (24h single patch test, 2005) the undiluted Docosyl docosanoatewas applied to the back skin of 11 volunteers for 24 h under occlusive conditions. The skin irritation effects (erythema and edema) were assessed 30 minutes and 24 h after patch removal. Slight to moderate erythema (score 1-1.5) was observed at the test site in 3/10 subjects at the 30-minute reading time point and in 1/10 subjects 24 h after patch removal. The positive control (1% sodium sulphate) was shown to be valid. 1/11 subjects were excluded as moderate erythema was noted at the negative control site (water).

 

 

Eye irritation

CAS 90990-29-7

The eye irritation potential of Fatty acids, C16 and C18-22 - unsatd., C16-18 and C18 unsatd. alkyl ester was investigated in six albino rabbits, following a protocol similar to OECD guideline 405 (Key, 1982) and in compliance with GLP. 0.1 g of the test substance was instilled into one eye of each animal. The other eye remained untreated and served as control. The eyes were examined and scored according to the Draize scoring system 24, 48 and 72 h after application.

3/6 animals showed conjunctival redness (score 1) 24 and 48 h after instillation, reversible within 72 h. 2/6 animals showed conjunctivae chemosis (score 1) 24 h after instillation of test substance, in one animal reversible within 48 h, in the second animal reversible within 72 h. The cornea and iris were not affected. The mean 24/48/72 h scores of all 6 animals for redness were 0.0, 0.67, 0.67, 0.0, 0.0 and 0.67, respectively , while mean 24/48/72 h scores for chemosis were 0.67, 0.0, 0.0, 0.0, 0.0 and 0.33,respectivley. Based on the results of this study, the test substance is not considered to be irritating to the eyes. 3/6 animals showed conjunctival redness (grade 1) 24 and 48 h after instillation, reversible within 72 h. 2/6 animals showed conjunctivae chemosis (grade 1) 24 h after instillation of test substance, in one animal reversible within 48 h, in the second animal reversible within 72 h.

Overall conclusion for skin and eye irritation

The available data on the target and source substances did not show any skin or eye irritation effects. Therefore, the target substance Fatty acids, C16 and C18-22 - unsatd., C16-18 and C18 unsatd. alkyl ester (CAS 90990-29-7) is not considered to be a skin irritant .The data on eye irritation indicates that Fatty acids, C16 and C18-22 - unsatd., C16-18 and C18 unsatd. alkyl ester is not an eye irritant.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to Fatty acids, C16 and C18-22 - unsatd., C16-18 and C18 unsatd. alkyl ester (CAS 90990-29-7), data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

 

Therefore, based on the target substance information and analogue read-across approach, the available data on skin and eye irritation do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are therefore conclusive but not sufficient for classification.