Fatty acids, C5-9, hexaesters with dipentaerythritol

Endpoint summary

Description of key information

Skin irritation/corrosion: not irritating (OECD 404, analogue approach)
Eye irritation: not irritating (OECD 405, analogue approach)

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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions. (Limited documentation but relevant data given)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

limited documentation but relevant data given

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 5.0 - 5.2 g

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

4 d
Reading time points: 30 - 60 min, 24, 48, 72 and 96 h

Number of animals:

3 (females)

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm

REMOVAL OF TEST SUBSTANCE
- Washing (if done): cleansing with clean warm water
- Time after start of exposure: 4 h (upon removal of the dressing)

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: mean over 24 h, 48 h and 72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 4 d

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: mean over 24 h, 48 h and 72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 4 d

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: mean over 24 h, 48 h and 72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 4 d

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: mean over 24 h, 48 h and 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: mean over 24 h, 48 h and 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: mean over 24 h, 48 h and 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Table 1: Erythema scores

Animal Number	24 hours	48 hours	72 hours	96 hours	Mean Score
26	2	1	1	0	1.3
35	2	2	1	0	1.7
36	2	1	1	0	1.3

 

Table 2: Edema Score

Animal Number	24 hours	48 hours	72 hours	96 hours	Mean Score
26	1	0	0	0	0.3
35	1	0	0	0	0.3
36	1	0	0	0	0.3

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: 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:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions (lack of data on test substance and animal husbandry).

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

(lack of details on test substance and animal husbandry)

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 3.6 - 4.6 kg

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

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

Duration of treatment / exposure:

single application without washing

Observation period (in vivo):

3 d

Number of animals or in vitro replicates:

3 females

Details on study design:

SCORING SYSTEM: Draize scoring system

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

out of all three animals

Time point:

other: mean over 24 h, 48 h and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

out of all three animals

Time point:

other: mean over 24 h, 48 h and 72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility not applicable

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

out of all three animals

Time point:

other: mean over 24 h, 48 h and 72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility not applicable

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

out of all three animals

Time point:

other: mean over 24 h, 48 h and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritant / corrosive response data:

No corneal or iridial effects were observed. Conjunctival effects included slight redness (1 animal) and slight discharge (1 animal) and were transiently seen approx. 1 h after dosing.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

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 no data available on the skin and eye irritation potential of the substance Fatty acids C5-9 esters with dipentaerythritol (CAS# 67762-52-1). In order to fulfil the standard information requirements set out in Annex VIII, 8.2, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances 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 for human toxicity, 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, Item 1.5, of Regulation (EC) No 1907/2006, whereby toxicological properties may be predicted from data for the reference substance(s) on the basis of structural similarity, the substances listed below are selected as reference substances for assessment of toxicological endpoints, for which information gaps are identified.

 

Overview for skin and eye irritation/corrosion

CAS	Skin Irritation/Corrosion	Eye Irritation/Corrosion
67762-52-1(a)	RA: CAS 68424-31-7	RA: CAS 68424-31-7
68424-31-7	Not irritating	Not irritating

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

 (b) Substances that are either already registered under REACh or not subject to the REACh  Phase-in registration deadline of 31 May 2013 are indicated in normal font.

 

The above mentioned substances are considered to be similar on the basis of structural similarity resulting in similar properties and/or activities. The available endpoint information is used to predict the same endpoints for Fatty acids, C5-9, hexaesters with dipentaerythritol (CAS# 67762-52-1).

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

 

Skin Irritation

Since no studies investigating the skin irritation of Fatty acids, C5-9, hexaesters with dipentaerythritol (CAS# 67762-52-1) are available, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across from the structurally related analogue substance Fatty acids, C5-10, esters with pentaerythritol (CAS# 68424-31-7) was conducted.

Skin irritation - Animal Data

CAS 68424-31-7

 

Three primary skin irritation studies were conducted to assess the skin irritation potential of Fatty acids, C5-10, esters with pentaerythritol (CAS# 68424-31-7)

In the first primary skin irritation study comparable to OECD Guideline 404 (Robinson, 1991a) the shaved skin of three female New Zealand White rabbits was exposed to 0.5 mL unchanged test substance for 4 hours under semiocclusive conditions. Skin reactions were assessed according to Directive 67/548/CEE approx. 1, 24, 48, 72 and 96 hours after removal of the test substance. The exposure period of 4 hours caused slight edema (score = 1) in all animals 24 hours after removal of the test substance which was completely reversed within 48 hours. Erythema was seen at the test site of one animal (score = 2) and slight at the test site of the other two animals (score =1). Erythema reactions were completely reversed within 96 hours after removal of the test substance in all three animals. All treated skin sites appeared normal at the 96 hour observation.

 

Two further primary dermal irritation studies were conducted with 0.5 mL test substance on the shaved skin of 3 male New Zealand White rabbits comparable to OECD Guideline 404 (Robinson, 1991b + c). Skin reactions were assessed according to Draize score approx. 1, 24, 48, 72, 96 hours and 7, 8 and 12 days after removal of the test substance. Following the single 4-hour application in the first study, moderate to severe erythema (maximum score = 4) and moderate to severe edema (maximum score = 4) were observed for 2 or 3 days after application in all animals. This regressed and no signs of erythema or edema were evident 4 to 12 days after application. Thickening of the skin at the application site was seen on one animal between 4 and 7 days after application. No other signs of irritations were observed. For the second study, following the single 4-hour application, very slight to well-defined erythema and very slight to slight oedema were observed in all animals (maximum score = 2). This regressed and no signs of erythema or oedema were evident 11 or 12 days after application. Slight desquamation at the application site of one animal was observed 7 days after application.

 

The test material is not considered irritating to the skin in these studies.

 

Eye irritation

Since no studies investigating the eye irritation of Fatty acids, C5-9, hexaesters with dipentaerythritol (CAS# 67762-52-1) are available, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across from the structurally related analogue substances Fatty acids, C5-10, esters with pentaerythritol (CAS# 68424-31-7) was conducted.

 

CAS 68424-31-7

An acute eye irritation study was performed with Fatty acids, C5-10, esters with pentaerythritol (CAS# 68424-31-7) according to OECD Guideline 405 (Robinson, 1991). 0.1 mL of the undiluted test substance was instilled into the conjunctival sac of one eye of three New Zealand White rabbits. The animals were observed for 72 hours. Eye irritation was scored according to the method of Draize 24, 48 and 72 hours after application. No corneal or iridial effects were observed. Conjunctival effects included slight redness (1 animal) and slight discharge (1 animal) and were transiently seen approx. 1 h after dosing.

 

Conclusion for skin and eye irritation

In conclusion,the tested structural analogue Fatty acids, C5-10, esters with pentaerythritol (CAS# 68424-31-7) showed no skin and eye irritation potential. Therefore, based on this result, no classification for skin and eye irritation for Fatty acids, C5-9, hexaesters with dipentaerythritol (CAS# 67762-52-1) is required.

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

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

Justification for classification or non-classification

Based on read-across from the structurally similar substances, the available data on skin/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.