Fatty acids, coco, iso-Bu esters

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

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 oral acute toxicity has been investigated using a grouping of substance and read across approach. All available acute oral toxicity studies within this category resulted in an acute oral 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: oral

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions (analytical purity of the test substance not provided, juvenile animals, only 2 animals used per sex and dose)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

analytical purity of the test substance not provided, juvenile animals, only 2 animals used per sex and dose

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Weight at study initiation: males: 178 g; females: 150 g
- Fasting period before study: yes, animals were fasted 16 hours prior administration and 3 hours after application
- Housing: 2 animals were housed in Makrolon 3 cages
- Diet: Altromin-Haltungsdiät 1324, Altromin GmbH, Lage, Germany, ad libitum
- Water: tap-water ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 25
- Humidity (%): 45 - 60
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

oral: gavage

Vehicle:

peanut oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20% (g/v)
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

2

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Animals were observed several times on the day of dosing and 2 times per day thereafter. Individual body weights were determined daily prior and on the day of application, on Day 7 and Day 14 after application
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortalitites or clinical sigsn of adverse systemic toxicity observed at this concentration.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: No signs of systemic toxicity were observed during the 15-day observation period. Only slight pilo-erection was observed 1 - 2.5 hours after application.

Gross pathology:

No findings considered to be related to treatment.

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: supporting information

Reference

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

weight of evidence

Study period:

30 Dec 1992 - 13 Jan 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions; no details on test substance given.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

lack of details on test substance

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Evic Ceba, Blanquefort, France
- Age at study initiation: 4 weeks
- Weight at study initiation: 18.5 - 20 g
- Fasting period before study: yes the day before treatment
- Housing: 5 by sex and cage, in polypropylene cages (46.5 x 15 x 14 cm)
- Diet: grained diet, UAR A04 (Epinay Sur Orge, France), ad libitum
- Water: ad libitum

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: maize oil was used as vehicle and the concentration of test substance in vehicle was 500mg/mL.
- Amount of vehicle (if gavage): 10 mL/kg bw

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations for clinical signs started one hour after application, and were done hourly during the first 5 hours; thereafter, these observations were conducted at least once daily until the end of the observation period. Weighing was done at test starting and at day 3, 7 and 14.
- Necropsy of survivors performed: yes, at the end of the observation period, the animals were sacrificed for the purpose of necropsy and subjected to gross pathological examination.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: No clinical signs of toxicity were observed up to the end of the observation period.

Gross pathology:

Necropsy revealed no substance-related findings.

Table 1: Body weight and body weight change

Body weight (g) and body weight change (g) in mice treated by single gavage with the test substance in maize oil
Sex	animal	Day 0	Day 3	Day 7	Day 14	Day 0 to 14
Males	1	19.5	23	26	31	11.5
	2	20	25	29	33	13
	3	19	24	27	32	13
	4	20	24	27	31	11
	5	19	24	26.5	30	11
	mean	19.5	24	27.1	31.4	11.9
Females	1	19	24	25	28	9
	2	19	23	25	27	8
	3	19	21	22	25	6
	4	18.5	21	23	26	7.5
	5	19.5	23	25	27	7.5
	Mean	19	22.4	24	26.6	7.6

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:

test mat.

Remarks on result:

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 oral toxicity studies within this category resulted in an acute oral 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 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. All available acute oral toxicity studies within this category resulted in an acute oral 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) .