Docosyl stearate

Endpoint summary

Description of key information

Skin, rabbit: not irritating

Skin, rabbit: not irritating (read-across from CAS 93803-87-3, WoE)

Eye, rabbit: not irritating (read-across from CAS 93803-87-3, key)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

07 Sep - 24 Nov 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 2002

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 2015

Deviations:

no

GLP compliance:

no

Remarks:

The study was conducted to meet the requirement of a regulation (Japan) other than Regulation (EC) No. 1907/2006 and therefore not conducted according to GLP.

Species:

rabbit

Strain:

other: Japanese White rabbits (Jla:JW)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: JLA, INC.
- Age at study initiation: 18 weeks
- Weight at study initiation: 2.94 - 3.38 kg
- Housing: The animals were individually housed in aluminium cages (W 560 x D 550 x H 410 mm) and given a plastic chain (polyethylene) as the environmental enrichment.
- Diet: RC4 pelleted diet (Oriental Yeast Co., Ltd., Lot No. 160518 and 160613), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: Yes, 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 24
- Humidity (%): 42 - 66
- Air changes (per hr): 11 - 14
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 07 Sep 2016 To: 24 Nov 2016

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

yes, concurrent vehicle

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 g

VEHICLE
- Amount(s) applied: 0.5 mL

Duration of treatment / exposure:

Initial test: 3 min, 1 and 4 h
Confirmatory test: 4 h

Observation period:

1, 24, 48 and 72 h

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap: At the 3-min and 1-h exposure duration, the applied lint patch was covered with a tape [Tegaderm (3M Health Care)]. At the 4-h exposure duration, the applied lint patches (control and test substance) were covered with an elastic bandage [3M Coban Self-Adherent Wrap (3M Health Care)] and fixed with polyethylene film tape [KEEPPORE A (Nichiban Co., Ltd.)].

REMOVAL OF TEST SUBSTANCE
- Washing: The application sites were wiped with absorbent cotton soaked with water for injection [Lot No. 5J84 (Otsuka Pharmaceutical Factory, Inc.)].
- Time after start of exposure: 3 min, and 1 and 4 h, respectively

OBSERVATION TIME POINTS
1, 24, 48 and 72 h

SCORING SYSTEM:
- Method of calculation: Draize scoring system

Irritation parameter:

erythema score

Remarks:

4 h of exposure

Basis:

mean

Remarks:

of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Remarks:

1 h of exposure

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Remarks:

3 min of exposure

Basis:

animal #1

Time point:

other: 1 and 24 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Test was discontinued since no signs of skin icorrosion (full thickness necrosis) were observed.

Irritation parameter:

edema score

Remarks:

4 h of exposure

Basis:

mean

Remarks:

of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Remarks:

1 h of exposure

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Remarks:

3 min of exposure

Basis:

animal #1

Time point:

other: 1 and 24 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Test was discontinued since no signs of skin icorrosion (full thickness necrosis) were observed.

Irritant / corrosive response data:

There were no skin corrosive or irritating reactions on any application site of the test substance (sites for 3-min, 1-h or 4-h exposure) of any animal at any observation point.

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:

read-across from supporting substance (structural analogue or surrogate)

Remarks:

Summary of available data used for the endpoint assessment of the target substance

Adequacy of study:

key study

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of all 3 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Source: CAS 93807-87-3, 1998, RL1

Irritation parameter:

iris score

Basis:

mean

Remarks:

of all 3 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

other: Source: CAS 93807-87-3, 1998, RL1

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

not fully reversible within: 48 h

Remarks on result:

other: Source: CAS 93807-87-3, 1998, RL1

Irritation parameter:

conjunctivae score

Basis:

animal: #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Source: CAS 93807-87-3, 1998, RL1

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of all 3 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Source: CAS 93807-87-3, 1998, RL1

A further in vivo eye irritation study with CAS 72576-80-8 was available and used as supporting study, which resulted in negative results.

CAS 72576-80-8:

Cornea opacity score (mean of all 3 animals; 24/48/72 h): 0

Iris score (mean of all 3 animals; 24/48/72 h): 0

Conjunctivae score (24/48/72 h): 0.33 each for animal #1, #2 and #3; fully reversible within 48 h

Chemosis score (mean of all 3 animals, 24/48/72 h): 0

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation(EC) No. 1272/2008

Conclusions:

The available data on suitable source substances did not show any eye irritating effect. Therefore, the target substance docosyl stearate (CAS 22413-03-2) is not considered to be irritating towards the skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for read-across

Adequate data on the skin and eye irritation potential of docosyl stearate (CAS 22413-03-2) were not available. The assessment was therefore based on studies conducted with analogue substances 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/corrosion

CAS 22413-03-2

A skin irritation study was performed according to OECD 404 with docosyl stearate (CAS 22413-03-2) (Kannami Laboratory, 2016). The skin corrosive and irritating potential of docosyl stearate (CAS 22413-03-2) was examined in three female Japanese White rabbits. 0.5 g of the pulverized test substance was put on a lint patch and moistened with water for injection uniformly and applied to the dorsal skin of one animal, where fur was clipped, for 3 minutes, 1 hour or 4 hours (initial test). Since no skin corrosive reaction was observed in the initial test, application was conducted to two additional animals for 4 hours (confirmatory test). The same lint patch without test item was also applied as a control substance in 4-hour application in both tests. The skin reactions were observed at 1, 24, 48 and 72 hours after removal of the application (by 24 hours after removal of application in 3 minute-application in the initial test) and scored according to the Draize's criteria. The individual mean score was 0 each in erythema/eschar formation and edema formation.

CAS 93803-87-3

A study was performed according to OECD 404 to assess the skin irritation potential of 2-octyldodecyl isooctadecanoate (CAS 93803-87-3) (Notox, 1998b). 0.5 g test substance was applied to the shaved skin of rabbits under semi-occlusive conditions for 4 hours. 3/3 animals had well-defined erythema (score 2) at the 1-hr reading time point. The erythema had reduced in severity by 24 hours after exposure in 3/3 rabbits (score 1, 1, 1), and had cleared completely within 72 hours for 3/3 rabbits. The mean score for the 24, 48 and 72 evaluation times was 0.67, 0.33 and 0.33. No edema was observed in any animal at any time point.

CAS 17671-27-1

In a single exposure patch test, the undiluted test substance was applied to the back skin of 11 volunteers for 24 hours under occlusive conditions (BIO-HC, 2005). The skin irritation effects (erythema and edema) were assessed 30 minutes and 24 hours after patch removal. Slight to moderate erythema was observed at the test site in 3/10 subjects at the 30-minute reading time point and in 1/10 24 hours 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 72576-80-8

An eye irritation GLP study was performed with isooctadecyl palmitate (CAS 72576-80-8) according to OECD 405 (Cosmepar, 1999). 0.1 mL of the unchanged test substance was instilled into one eye of each of 3 male New Zealand White rabbits. The animals were observed for 7 days and scoring according to Draize was performed 1, 24, 48 and 72 hours, and 7 days after application. The eyes were not rinsed. At the 1-hour reading time point, 3/3 rabbits showed slight to moderate conjunctival redness (scores 1, 1, 2) and 2/3 showed slight chemosis (scores 0, 1, 1). The chemosis had cleared by the 24-hour reading time point, while 3/3 animals still had slight conjunctival redness (scores 1, 1, 1). All eye irritation effects were fully reversible within 48 hours. The individual mean cornea opacity, iris, and chemosis scores over 24/48/72 hours were 0.0 for each rabbit. The individual mean conjunctivae scores over 24/48/72 hours were 0.33, 0.33 and 0.33. The test substance did not cause eye irritation under the conditions of the study.

 

CAS 93803-87-3

2-octyldodecyl isooctadecanoate (CAS 93803-87-3) was examined for its eye irritation potential in a GLP study performed according to OECD 405 (Notox, 1998c). 0.1 mL of undiluted test liquid test substance was instilled into one eye of each of 3 rabbits. The animals were observed for 72 hours and scoring according to Draize was performed 1, 24, 48, and 72 hours after application. At the 1-hour reading time point 3/3 rabbits showed slight conjunctival redness (score 1, 1, 1), which was still present in 1/3 rabbits at the 24-hour reading time point. The effect had cleared completely within 48 hours. No other eye irritation effects were observed in any rabbit at any time point. The individual mean cornea opacity, iris, and chemosis scores over 24/48/72-hour readings were 0.0 for each rabbit. The individual mean conjunctivae scores over 24/48/72-hour readings were 0.33, 0 and 0. The test substance did not cause eye irritation under the conditions of the study.

Overall conclusion for skin and eye irritation

Based on the available data with the target and the source substances, no skin or eye irritation potential is expected for the target substance docosyl stearate (CAS 22413-03-2).

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 docosyl stearate (CAS 22413-03-2), 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.

 

The available data on skin and eye irritation do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.