Fatty acids, coco, iso-Bu esters

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The target substance FATTY ACIDS, COCO, ISO-BU ESTERS (CAS 91697-43-7) and the source substance FATTY ACIDS, C16-18, ISOBUTYL ESTERS (CAS 85865-69-6) are both Short Chain Alcohol Esters (SCAE C2-C8) composed by a fatty acid (C16-C18) and a C4 alcohol (isobutanol).
The source and the target substance show therefore the same reactive groups and a similar composition. A read-across to the source is therefore justified.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Both target and source substances are fatty acid esters produced by chemical reaction of an alcohol (isobutanol) with organic acids (e. g. stearic acid) in the presence of an acid catalyst. The esterification reaction is started by a transfer of a proton from the acid catalyst to the acid to form an alkyloxonium ion. The carboxylic acid is protonated on its carbonyl oxygen followed by a nucleophilic addition of a molecule of the alcohol to a carbonyl carbon of acid. An intermediate product is formed. This intermediate product loses a water molecule and proton to give an ester. Monoesters are the final product of esterification.

3. ANALOGUE APPROACH JUSTIFICATION
Since both target and source substances are fatty acid esters produced by chemical reaction of an alcohol (isobutanol) with an organic acid and therefore share similar/overlapping structural features and functional groups, it is justified to use a read across approach. The source substance has been registered already and its skin irritation potential has been investigated using a grouping of substance and read across approach. Based on the results of the available animal studies as well as according to the results on human skin, none of the substances within the fatty acid C2-8 ester category is considered skin irritating. Therefore, based on a weight of evidence approach, no classification for skin irritation for all substances within the fatty acid C2-8 esters category is required.
The same behaviour is predicted for the target substance FATTY ACIDS, COCO, ISO-BU ESTERS (CAS 91697-43-7) .

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

skin irritation: in vivo

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Study period:

04 - 07 Jan 2002

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP-guideline study with acceptable restrictions (analytical purity of test substance was not specified).

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

analytical purity of test substance not specified

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

analytical purity of test substance not specified

GLP compliance:

yes (incl. QA statement)

Remarks:

The Department of Health of the Government of the United Kingdom

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, UK
- Age at study initiation: 12 - 16 weeks
- Weight at study initiation: 2.0 - 3.5 kg
- Housing: individually in suspended matal cages
- Diet: ad libitum, certified rabbit diet (Code 5322, PMI Nutrition)
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

not specified

Controls:

other: not required, untreated sites of the same animal served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

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

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: cotton gauze patch secured in position with surgical adhesive patch


REMOVAL OF TEST SUBSTANCE
- Washing: with cotton soaked in 74% industrial methylated spirits
- 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:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48h

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72h

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72h

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48h

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48h

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48h

Irritant / corrosive response data:

Well-defined erythema was noted at all treated skin sites one hour after patch removal regressing to very slight erythema at all treated skin sites at the 24 h observation and two treated skin sites at the 48 h observation.
Slight edema was noted at all treated skin sites one hour after patch removal regressing to very slight erythema at all treated skin sites at the 24 h observation. One treated skin site appeared normal at the 48 h observation and the two remaining treated skin sites appeared normal at 72 h.

Erythema Score

Animal Number	24 h	48 h	72 h
1	1	0	0
2	1	1	0
3	1	1	0

 

Edema Score

Animal Number	24 h	48 h	72 h
1	1	0	0
2	1	0	0
3	1	0	0

 

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Cross-reference 2

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

skin irritation: in vivo

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Study period:

04 - 18 Feb 1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions (no experimental 48 h reading performed, only 72 hours observationperiod, 24 hours occlusive application, analytical purity of test substance not specified, limited documentation available).

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

occlusive dressing, 24 instead of 4 h exposure, no experimental 48 h reading performed, limited documentation, analytical purity of test substance not specified

Qualifier:

according to guideline

Guideline:

other: FHSA

GLP compliance:

not specified

Species:

rabbit

Strain:

other: Albino

Type of coverage:

occlusive

Preparation of test site:

other: shaved and abraded

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
- Concentration (if solution): undiluted

Duration of treatment / exposure:

24 hours

Observation period:

72 hours (as all signs of irritation were fully reversible)
Reading time points: 24 and 72 h

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: back skin, 2.5 cm x 2.5 cm
- Type of wrap if used: clear plastic trunk bands

SCORING SYSTEM: according to Draize

The animals were immobilized during the 24 hour exposure period.
Upon removal of the patches the resulting reactions were evaluated on the basis weighted scores. Evaluations were again made after 72 hours.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

24/48/72 h

Score:

0.22

Max. score:

4

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: no 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)

Irritation parameter:

edema score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Reversibility: not applicable

Remarks on result:

other: no 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)

Other effects:

The skin scores upon treatment of abraded skin were similar to intact skin.

Table 1: Results of skin irritation study

Observation time	Rabbit no.
	1		2		3		4		5		6
	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema
24 h	0	0	1	0	0	0	0	0	0	0	1	0
48 h	No experimental data available; for calculation of mean scores, the 48 h values were assumed to bet he same as those at 24 h (worst case assumption)
72 h	0	0	0	0	0	0	0	0	0	0	0	0

 

Table 2: Calculation of mean scores

	Rabbit no.
	1		2		3		4		5		6
	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema
Mean value 24 + 48 + 72 h	0.00	0.00	0.67	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.67	0.00

*No 48 h data are available: for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h). 

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Test material

Test material information

Constituent 1

Reference substance name:

Fatty acids, coco, iso-Bu esters

EC Number:

294-304-2

EC Name:

Fatty acids, coco, iso-Bu esters

Cas Number:

91697-43-7

Molecular formula:

Not available for UVCB substances

IUPAC Name:

Fatty acids, coco, iso-Butyl esters

Test material form:

liquid

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritant / corrosive response data:

Well-defined erythema was noted at all treated skin sites one hour after patch removal regressing to very slight erythema at all treated skin sites at the 24 h observation and two treated skin sites at the 48 h observation.
Slight edema was noted at all treated skin sites one hour after patch removal regressing to very slight erythema at all treated skin sites at the 24 h observation. One treated skin site appeared normal at the 48 h observation and the two remaining treated skin sites appeared normal at 72 h.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The source substance has been registered already and its oral acute toxicity has been investigated using a grouping of substance and read across approach. Based on the results of the available animal studies as well as according to the results on human skin, none of the substances within the fatty acid C2-8 ester category is considered skin irritating. Therefore, based on a weight of evidence approach, no classification for skin irritation for all substances within the fatty acid C2-8 esters category is required.
The same behaviour is predicted for the target substance FATTY ACIDS, COCO, ISO-BU ESTERS (CAS 91697-43-7) .

Executive summary:

The target substance FATTY ACIDS, COCO, ISO-BU ESTERS (CAS 91697-43-7) and the source substance FATTY ACIDS, C16-18, ISOBUTYL ESTERS (CAS 85865-69-6) are both Short Chain Alcohol Esters (SCAE C2-C8) composed by a fatty acid (C16-C18) and a C4 alcohol (isobutanol).

The source and the target substance show therefore the same reactive groups and a similar composition. A read-across to the source is therefore justified.

The source substance has been registered already and its oral acute toxicity has been investigated using a grouping of substance and read across approach. Based on the results of the available animal studies as well as according to the results on human skin, none of the substances within the fatty acid C2-8 ester category is considered skin irritating. Therefore, based on a weight of evidence approach, no classification for skin irritation for all substances within the fatty acid C2-8 esters category is required.

The same behaviour is predicted for the target substance FATTY ACIDS, COCO, ISO-BU ESTERS (CAS 91697-43-7) .