Fatty acids, C16-18 (even numbered), esters with 1,2-propanediol

Endpoint summary

Description of key information

Skin irritation/corrosion: not irritating (OECD 404, GLP)
Eye irritation: not irritating (OECD 405, GLP)
 
The hazard assessment is based on the data currently available. New studies with the registered substance and/or other member substances of the glycol esters category will be conducted in the future. The finalised studies will be included in the technical dossier as soon as they become available and the hazard assessment will be re-evaluated accordingly.
For further details, please refer to the category concept document attached to the category object (linked under IUCLID section 0.2) showing an overview of the strategy for all substances within the glycol esters category.

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:

16 Dec - 19 Dec 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

lack of experimental and test material details

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

lack of experimental and test material details

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Chesire, UK
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.19-2.49 kg
- Housing: individually housed in suspended metal cages
- Diet: Rabbit Diet (Preston Farmers Limited, New Leake, Boston, Lincolnshire, UK), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15-18
- Humidity (%): 55-65
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

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:

72 h
Reading time points: 1, 24, 48 and 72 h

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 6.25 cm² on the dorsal flank area
- Type of wrap if used: The treated skin was covered with a gauze patch and held in place with a strip of surgical adhesive tape. Additionally, the trunk of the animal was wrapped in an elasticated corset.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test material was removed by gently swabbing with cotton wool soaked in distilled water and diethyl ether.
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

edema score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritant / corrosive response data:

24 h after removal of the test substance slight erythema in 1/3 animals was observed which was fully reversible within 48 h. The remaining animals revealed no erythema formation. No edema was observed during the study period in any animal.

Other effects:

No further local or systemic effects were reported.

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

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

weight of evidence

Study period:

03 Jun -10 Jun 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

GLP-Guideline study, tested with the source substance Decanoic acid, mixed esters with octanoic acid and propylene glycol (CAS 68583-51-7). According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (Dec 2012)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: Kleinrusse Chbb:HM

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Thomae, Biberach, Germany
- Age at study initiation: adult animals
- Weight at study initiation: mean 2457.5 g
- Housing: single holding in cage
- Diet: Altromin-Haltungsdiät 2023 (Altomin GmbH, Lage, Germany), ad libitum
- Water: tap water, ad libitum
- Identification of animals: Ear tattoo and cage labelling
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21
- Humidity (%): 45-55
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

single application without wasching

Observation period (in vivo):

72 h
Reading time points: 1, 6, 24, 48 and 72 h

Number of animals or in vitro replicates:

4 males

Details on study design:

PRELIMINARY CONTROL:
The eyes of the animals were visually controlled and with fluorescein, 24 h prior to application.

MAIN STUDY:
A control of the treated eye with fluorescein was conducted, 24 h after application and after macroscopic control of the eye.

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2, #3 and #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

iris score

Basis:

animal: #1, #2, #3 and #4

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal: #1, #2, #3 and #4

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility not applicable

Irritation parameter:

chemosis score

Basis:

animal: #1, #2, #3 and #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritant / corrosive response data:

Cornea: no effects were observed during the study period in any animal.
Iris: no effects were observed during the study period in any animal.
Conjunctivae: after 1 h mild redness was observed in 2 of 4 animals. In one of theses animals the effect was fully reversible within 6 h after application. The second animal showed mild redness until 6 h after application being fully reversible after 24 h as well.
Chemosis: no effects were observed during the study period in any animal.
Exudation: no effects were observed during the study period in any animal.

Other effects:

No further local or systemic effects were reported.

Interpretation of results:

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

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

weight of evidence

Study period:

21 May - 24 May 1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

GLP-Guideline study, tested with the source substance Fatty acids, C14-18 and C16-18-unsatd., esters with propylene glycol (CAS 84988-75-0). According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (Dec 2012)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: Kleinrussen, Chbb:HM

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Thomae, Biberach, Germany
- Age at study initiation: 4 months
- Weight at study initiation: 2370 g
- Housing: individually housed in cages (E. Becker & Co)
- Diet: Ssniff rabbit diet K4 Charge: 66029126 (Ssniff GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 45-70
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

24 h

Observation period (in vivo):

72 h
Reading time points: 1, 24, 48 and 72 h

Number of animals or in vitro replicates:

3 male

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated eye was rinsed with tepid tap water.
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize scoring system

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

iris score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritant / corrosive response data:

Cornea/ Iris: No effects on cornea/iris were observed in any animal during the study period.
Conjunctivae: After 1 and 24 h 2/3 animals showed slight erythema being fully reversible within 48 h.
Chemosis: In 1/3 animals slight chemosis was observed after 1 h being fully reversible within 24 h. No further edema formation was observed during the study period in any animal.

Other effects:

No further local or system effects were reported.

Table 1. Results of eye irritation study.

Rabbit #	Time [h]	conjunctivae		iris	cornea
		redness	swelling
1	1	0	0	0	0
	24	0	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.0	0.0	0.0	0.0
2	1	1	0	0	0
	24	1	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.3	0.0	0.0	0.0
3	1	1	1	0	0
	24	1	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.3	0.0	0.0	0.0
	Time [h]	conjunctivae		iris	cornea
		redness	swelling
average score	1	0.67	0.33	0.00	0.00
	24	0.67	0.00	0.00	0.00
	48	0.00	0.00	0.00	0.00
	72	0.00	0.00	0.00	0.00
	24+48+72	0.22	0.00	0.00	0.00

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

Irritation

The hazard assessment is based on the data currently available. New studies with the registered substance and/or other member substances of the glycol esters category will be conducted in the future. The finalised studies will be included in the technical dossier as soon as they become available and the hazard assessment will be re-evaluated accordingly.

For further details, please refer to the category concept document attached to the category object (linked under IUCLID section 0.2) showing an overview of the strategy for all substances within the glycol esters category.

 

Skin Irritation

CAS 68583-51-7

The skin irritation properties of Decanoic acid, mixed diesters with octanoic acid and propylene glycol were tested in a study according to OECD 404 in compliance with GLP (Safepharm Laboratories Ltd., 1989). In the study, 3 New Zealand White rabbits were exposed to 0.5 mL of the undiluted test substance, applied to the shaved skin for 4 h using a semiocclusive dressing. The treated skin was observed and evaluated at 1, 24, 48 and 72 h post-application. In 1/3 animals 24 h after removal of the test substance, slight erythema (score 1) was observed which was fully reversible within 48 h (mean erythema score 0.3 over 24, 48 and72 h). The remaining animals revealed no erythema formation. No edema formation or further local or systemic effects were apparent in any animal during the study period.

 

In summary, Decanoic acid, mixed diesters with octanoic acid and propylene glycol is not irritating to the skin.

 

Furthermore, Propylene Glycole Stearate induced no or only mild irritation to skin (Cosmetic Ingredient Review, 1983).

 

Eye irritation

CAS 68583-51-7

The eye irritation properties of Decanoic acid, mixed diesters with octanoic acid and propylene glycol were tested in a study according to OECD 405 in compliance with GLP (Henkel, 1988).

In a group of 4 male rabbits (Kleinrusse), 0.1 mL of the undiluted test substance was applied into one eye, in a single application without washing. The eyes were observed and reactions were evaluated 1, 6, 24, 48 and 72 h after application. No effects on corneal opacity and iris were noted at any time point in any animal. However, mild conjunctival redness was observed in 2/4 animals at the 1 h reading time point. In one of these animals the effect was fully reversible within 6 h; in the second animal mild redness was apparent until 6 h after application being fully reversible after 24 h as well (mean score over 24, 48 and 72 h out of all 4 animals = 0). No chemosis or exudation were observed during the study period in any animal. No further local or systemic effects were observed in any animal during the study period.

Based on the obtained resluts, Decanoic acid, mixed diesters with octanoic acid and propylene glycol is not eye irritating.

 

CAS 84988-75-0

The eye irritation properties of Fatty acids, C14-18 and C16-18 unsaturated, ester with propylene glycol were tested in a study performed according to OECD guideline 405 (Henkel, 1991). 0.1 mL of the unchanged test substance was applied into the eye of 3 rabbits (Kleinrussen, Chbb:HM). The untreated eye served as control. After 24 h, the treated eye was rinsed with teptid tap water. Observation of the eyes was performed 1, 24, 48 and 72 h after application. No effects on cornea and iris were noted in any animal during the study period. However, slight erythema being fully reversible within 48 h (score 0.33 calculated over 24, 48 and 72 h) were observed in 2/3 animals. In 1/3 animals, slight chemosis was observed after 1 h being fully reversible within 24 h. No further edema formation was observed during the study period in any animal. In addition, no systemic effects were observed in any animal during the study period. Therefore, Fatty acids, C14-18 and C16-18 unsaturated, ester with propylene glycol is considered as not irritating.

 

Furthermore, Propylene Glycole Stearate induced no or only minimal eye irritation (Cosmetic Ingredient Review, 1983).

 

Conclusion on skin and eye irritation properties

Skin and eye irritation properties of the read-across analogue substances have been investigated in vivo indicating no irritating properties towards the skin or eyes. Therefore, based on these data, Octadecanoic acid, monoester with 1,2-propanediol (CAS 1323-39-3) and Palmitic acid, monoester with propane-1,2-diol (CAS 29013-28-3) is not considered as skin or eye irritant.

Justification for classification or non-classification

Based on the analogue read-across approach, the available data on skin and eye irritation 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.