Bis(16-methylheptadecyl) malate

Endpoint summary

Description of key information

Skin irritation (similar to OECD 404), rabbit: not irritating 
Eye irritation (similar to OECD 405), rabbit: 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:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

no analytical purity and clinical signs reported; environmental condition (temperature range) differs from the temperature recommended in the appropriate OECD guideline

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, Prouzel, France
- Age at study initiation: adult animals
- Weight at study initiation: 2200 - 3500 g
- Housing: the animals were housed individually in polystyrene cages.
- Diet: granulated diet 112 C (U.A.R., Villemoisson-sur-Orge, France), ad libitum
- Water: filtered tap water, ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated sites of the same animal served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 mL

Duration of treatment / exposure:

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

Observation period:

7 days
Reading time points: 1, 24, 48 and 72 h and 4 days

Number of animals:

3 males (main test)
1 male (initial test)

Details on study design:

TEST SITE
- Area of exposure: 6 cm² on one site of the dorsal/flank area
- Type of wrap if used: The test item was introduced under a patch which was secured in position with a hypoallergenic medical plaster.

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: mean after 24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: mean after 24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: mean after 24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

edema score

Basis:

mean

Remarks:

of 3 animals

Time point:

other: mean after 24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicablereversibility: not applicable

Irritant / corrosive response data:

In an initial test slight erythema formation (grade 1) was noted in one animal 1 h after patch removal and remained 48 h after patch removal and was fully reversible within 72 h. No edema formation was observed. Slight erythema formation (grade 1) was noted in 3/3 animals 1 h after patch removal and remained in all animals 24 h after patch removal. Erythema formation was fully reversible within 48 h in 2/3 animals and 4 days in 1/3 animals. No edema formation was recorded in any animal.

Table 1: Summary of individual skin irritation after 3 min and 4 h exposure in one rabbit (initial test)

Observation time	Rabbit no.
	1
	Erythema	Edema
1 h	1	0
24 h	1	0
48 h	1	0
72 h	0	0
Mean value 24+48+72 h	0.67	0

Table 2: Summary of individual skin irritation scores after 4 h exposure (main test)

Observation time	Rabbit no.
	1		2		3
	Erythema	Edema	Erythema	Edema	Erythema	Edema
1 h	1	0	1	0	1	0
24 h	1	0	1	0	1	0
48 h	1	0	0	0	0	0
72 h	1	0	0	0	0	0
Mean value 24+48+72 h	1	0	0.33	0	0.33	0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

no analytical purity and clinical signs reported; environmental condition (temperature range) differs from the temperature recommended in the appropriate OECD guideline

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, Prouzel, France
- Age at study initiation: adult animals
- Weight at study initiation: 2200 - 3500 g
- Housing: the animals were housed individually in polystyrene cages.
- Diet: granulated diet 112 C (U.A.R., Villemoisson-sur-Orge, France), ad libitum
- Water: filtered tap water, ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 30 - 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: 0.1 mL

Duration of treatment / exposure:

single application without washing

Observation period (in vivo):

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

Number of animals or in vitro replicates:

3 males

Details on study design:

SCORING SYSTEM: Draize scoring system

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

other: mean after 24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

other: mean after 24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

other: mean after 24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility: not applicable

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

other: mean after 24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritant / corrosive response data:

Neither corneal nor iris effects were noted after application with the test material in all animals during the study period. Chemosis and conjunctivae (redness) effects (grade 1) were recorded in 3/3 animals 1 h after application with the test material. These effects were fully reversible within 24 h in 3/3 animals.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Discussion

Reliable data on skin and eye irritation is available with Diisooctadecyl malate (CAS 67763-18-2). 

Skin irritation

The skin irritation properties of Diisooctadecyl malate (CAS 67763-18-2) were tested in a reliable in vivo skin irritation study performed similar or equivalent to OECD TG 404 (Jouffrey, 1995a). In the study 0.5 mL test substance was applied to the shaved skin of one New Zealand White rabbits in an initial test for 3 min and 4 hours using a semi-occlusive dressing. As only slight erythema formation (grade 1) was recorded 1 - 48 h after application of the test material (being fully reversible within 72 h) the same animal and two additional animals were exposed to 0.5 mL of the test material for 3 min and 4 h. The treated skin of animals exposed to the test material for 4 h was observed and evaluated at 1, 24, 48 and 72 h and 4 days post-application. Slight erythema formation (grade 1) was noted in 3/3 animals 1 h after patch removal and remained in all animals 24 h after patch removal. Erythema formation was fully reversible within 48 h in 2/3 animals and 4 days in 1/3 animals. No edema formation was recorded in any animal. Thus, the test substance is considered to be non-irritating under the conditions of the test.

In the skin irritation study with Diisooctadecyl malate (CAS 67763-18-2) performed according to OECD TG 404 (Dufour, 1988b) three New Zealand White rabbits of unknown gender were treated with the test material and the treated skin was observed and evaluated for 72 h. After the observation period one moderate (grade 2) and one slight (grade 1) erythema was found after treatment of the animals. In addition, a very slight edema (grade 1) was observed, which was fully reversible at the 72 h observation time point, whereas one erythema (grade 1) was still present 72 h after exposure. No erythema and edema scores for each individual animal are reported. No test material purity and only limited information on the study design are available. Moreover, as effects were still present at the 72 h reading time point reversibility cannot be assessed. Thus, the available information is insufficient for assessment.  

Eye irritation

The eye irritation properties of Diisooctadecyl malate (CAS 67763-18-2) have been investigated in an in vivo study performed similar or equivalent to OECD TG 405 (Jouffrey, 1995b). For the assessment of the eye irritation properties 0.1 mL of the test substance was instilled in the eye of three male New Zealand White rabbits. The untreated eye of each animal served as control. The eyes were examined and the changes were graded according to the Draize scoring system 1, 24, 48 and 72 hours post-application. Neither corneal nor iris effects were noted after application with the test material in all animals during the study period. Chemosis and conjunctivae (redness) effects (grade 1) were recorded in 3/3 animals 1 h after application of the test material. These effects were fully reversible within 24 h in 3 3 animals. Based on the results of the study the test material is considered to be non-irritating to 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).

Justification for selection of eye irritation endpoint:
The reliable and comparable OECD Guideline study was choosen.

Justification for classification or non-classification

The available data on irritation/corrosion of the registered substance do not meet the criteria for classification according to Regulation (EC) No. 1272/2008, and are therefore conclusive but not sufficient for classification.