Fatty acids, coco, iso-Bu esters

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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 dermal acute toxicity has been investigated using a grouping of substance and read across approach. All available acute dermal toxicity studies within this category resulted in an acute dermal LD50 > 2000 mg/kg bw. It has been concluded that no adverse effects are observed for Fatty acids, C16-18, isobutyl esters (CAS No. 85865-69-6).
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:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

weight of evidence

Study period:

17 Sep - 01 Oct 2003

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

analytical purity of test substance not specified

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

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

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, UK
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: at least 200 g (± 20%)
- Fasting period before study: No
- Housing: individually in solid floor polypropylene cages during treatment and in groups of 5 thereafter
- Diet: ad libitum (Certified Mouse and Rat Diets, Code 5LF2, International Product Supplies Limited, UK)
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back and flanks
- % coverage: 10
- Type of wrap if used: surgical gauze fixed with self-adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing: cotton wool moisted with distilled water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: 2.26 mL/kg bw
- Constant volume or concentration used: yes

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 4 times on day of treatmentand subsequently once daily
- Necropsy of survivors performed: yes
- Other examinations performed: body weight on days 7 and 14.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortalities observed at the highest dose tested

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: No signs of systemic toxicity and no signs of dermal irritation were observed up to the end of the observation period.

Gross pathology:

Necropsy revealed no substance-related findings.

Interpretation of results:

not classified

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 source

Reference

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

weight of evidence

Study period:

16 Jun - 30 Jun 2010

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP guideline study, tested with the source substance CAS 544-35-4. According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, 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 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Wistar, Crl:WI (Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: approx. 10 weeks old
- Mean Bodyweight at study initiation: Males: 294 g, Females: 205 g. Body weight variation did not exceed +/- 20% of the sex mean.
- Housing: individually in Makrolon cages (MIII type, height 18 cm), containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
- Diet: pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany), ad libitum.
- Water: tap water, ad libitum.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0 (actual range: 19.9 - 21.5)
- Humidity (%): 40-70 (actual range: 39 - 75)
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back skin, clipped one day before exposure
- % coverage: approx. 10% of the total body surface (are of approx. 25 cm² for males and 18 cm² for females)
- Type of wrap if used: The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch, successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing: dressings were removed and the skin cleaned of residual test substance using tap water

TEST MATERIAL
- Amount(s) applied: 2000 mg/kg (2.27 mL/kg) body weight. Dose volume calculated as dose level (g/kg) /density (g/mL).
In order to obtain homogeneity, the test substance (formulations) were heated in a water bath with a maximum temperature of 39.5 ºC for a maximum of approximately 10 minutes.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Mortality/Viability: Twice daily;
Body weights Days 1 (pre-administration), 8 and 15;
Clinical signs at periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: yes, at the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Chromodacryorrhoea was shown by two animals on Day 1. Other clinical signs were not noted in any of the animals. The application site did not display any signs of skin irritation.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Materials and methods

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

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

other: LC50 value chosen as worst case value from all study results available

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. All available acute dermal toxicity studies within this category resulted in an acute dermal LD50 > 2000 mg/kg bw. It has been concluded that no adverse effects are observed for Fatty acids, C16-18, isobutyl esters (CAS No. 85865-69-6).
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 substance has been registered already and its oral acute toxicity has been investigated using a grouping of substance and read across approach. All available acute dermal toxicity studies within this category resulted in an acute dermal LD50 > 2000 mg/kg bw. It has been concluded that no adverse effects are observed for Fatty acids, C16-18, isobutyl esters (CAS No. 85865-69-6).

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