Isotridecyl 3,5,5-trimethylhexanoate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

6 May 1992 - 20 May 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

acute toxicity: dermal

Type of 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:

comparable to guideline study with acceptable restrictions

Remarks:

Read-across to similar substance.

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
Full details of the read-across justification are contained in the attached document.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The source and target substances are composed of the same chemical groups and are bonded together in functionally the same way. The source substance and target substances have similar molecular weight ranges, low water solubility, high partition coefficient, and are in the physical form of a liquid with a neutral pH. Available toxicity information on the source and target substances indicates that they behave in substantially similar ways in the body. The potential for acute dermal toxicity is therefore the same in both substances.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The source substance and target substances have branched acid groups, which are formed in the respective esters from mono-constituent acids (2-ethyl hexanoic acid for C12-15 Alkyl Ethylhexanoate, 3,5,5-trimetylhexanoic acid for both target substances). The alcohol parts of all three substances are also branching – each substance has an alcohol branch in which the chains are present as a variety of branched species. The slight difference is that whilst Isodecyl 3,5,5-trimethylhexanoate and Isotridecyl 3,5,5-trimethylhexanoate both have a set number of carbons in their alcohol chains (ten and thirteen respectively), the number of carbons in the C12-15 Alkyl Ethylhexanoate is variable (twelve to fifteen).
The alcohol part of the source substance contains an odd number of carbons, which is only shared with the target substance Isotridecyl 3,5,5-trimethylhexanoate, as Isodecyl 3,5,5-trimethylhexanoate has an even number of carbons in the alcohol. It is worth noting that due to the variation in the alcohol carbon amount in C12-15 Alkyl Ethylhexanoate, it also feasibly contains an even amount of carbons (as there will be species with twelve carbons and fourteen carbons) – which is a shared structure similarity to Isodecyl 3,5,5-trimethylhexanoate.
The acid part of the source substance has an even number of carbons, compared to both target substances that both have an odd number of carbons. Neither the source substance nor the target substances have hydrogen donor or hydrogen acceptor sites. The source substance and the target substances are fully saturated, with two hydrogens for every carbon. The molecular weights are very similar, and this means that the physical-chemical properties of the substances are very much alike (see Table 3), in particular:
• All are water insoluble (<0.2 mg/mL)
• All are liquids at room temperature with melting points <-35°C
• All have a boiling point or exothermic reaction at >300°C
• All have a relative density of 0.85-0.86 g/cm3
• All have high partition coefficients (Log KoW) of >7.2 at 35 °C pH 7
The source substance and the target substances are also unclassified under 1278/2008 CLP regulation for both skin and eye irritation/corrosion. In addition, all the substances have an acute oral toxicity of >4300 mg/kg bw, which also means they are unclassified. This, as well as the similarities in acute toxicity, indicate that they will have similar bioavailability.

3. ANALOGUE APPROACH JUSTIFICATION
Due to the similarities of the source and target substances with regards to branching, odd and even numbered alkyl, acid chains, and physico-chemical properties, the target substances are expected to behave in a substantially similar manner in vivo.
The target substances are therefore predicted to fail to induce acute dermal toxicity in the OECD 402 study when conducted in the rat. By extension, the target substances are considered not to fulfil the criteria for acute dermal toxicity under the Classification, Labelling, and Packaging (CLP) regulation (1272/2008).

4. DATA MATRIX
Full details of the read-across justification are contained in the attached document.

Reason / purpose for cross-reference:

read-across source

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

GHS criteria not met

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

12 May 1981

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Hexanoic acid, 2-ethyl-, C12-15-alkyl esters

EC Number:

291-443-0

EC Name:

Hexanoic acid, 2-ethyl-, C12-15-alkyl esters

Cas Number:

90411-66-8

IUPAC Name:

Hexanoic acid, 2-ethyl-, C12-15-alkyl esters

Test material form:

liquid

Specific details on test material used for the study:

A sample of the test material was received in April 30, 1992 and identified with entry n. 1599/1.

Analysis:

No analysis was carried out on the sample as all relevant data was provided by the Sponsor.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Species: Rats
Strain: Wistar
N.: 10 (5 males and 5 females)
Weight: 200-300 g at the beginning of the study
Sex: Males and Females
Supplier: Morini - S. Polo d'Enza (RE) - ITALY -

These rats were chosen as they are of the 2 species recommended by the Ministerial decree of December 5, 1983 and by OECD Guidelines and also because they are the same species used in the other toxicity test (oral).

- Caging:
The animals were caged in groups of 5 of the same gender in transparentpolycarbonate cages (dimensions mm 425x266x180h) .
The housing room was mantained under the following conditions:
Temperature: 20°C ± 2°C
Humidity: 55% ± 15%
R.H.: air was changed at least 25 times per hour and maintained at a pressure higher than the outside atmosphere
Artificial lighting: 12 h!day

- Cleaning and disinfection:
The cages and the housing room were cleaned and disinfected before the animals were accomodated, then cleaning and disinfection were performed periodically.

- Feeding:
Animals were fed with standard pellet complete diet supplied .by the authorized breeder Morini.

- Watering:
Filtered tap water from local network was supplied ad libitum.

- Animal identification:
Each animal was identified with an indelible colouring in different parts of the body.
No sign: 1
Head: 2
Back: 3
Tail: 4
Head + tail: 5

Cages were labelled.

- Quarantine:
Before being used in this study, the animals were kept in quarantine for one week. During this period they were observed daily. At the end of the quarantine week the animals were carefully examined in order to evaluate their suitability for the study.

- Animal selection:
The animals used for this study were selected randomly from those suitable, available at that time.

Administration / exposure

Type of coverage:

not specified

Vehicle:

other: Sesame oil

Details on dermal exposure:

- PREPARATION OF TEST MATERIAL:
A solution was prepared in sesame seed oil at a concentration of 200 mg/ml.

- EXPERIMENTAL DESIGN:
10 rats were used (5 males, 5 females).
No control group was used as it is documented that sesame seed oil is non toxic.
The animals were treated with a dose of 2000 mg/kg and was administered at a volume of 10 ml/kg.

- ADMINISTRATION:
The test material (10 ml/kg) was administered in one dose and applied directly on the skin.

Duration of exposure:

14 days

Doses:

The animals were treated with a dose of 2000 mg/kg which was administered at a volume of 10 ml/kg.
The test material (10 ml/kg) was administered in one dose and applied directly on the skin.

Control animals:

no

Details on study design:

All procedures followed during this study conform to the Biolab
S.G.S. Standard Operating Procedures, as recorded and shown in
the Biolab Procedures Manual.

Preparation of test material

A solution was prepared in sesame seed oil at a concentration of 200 mg/ml.

Experimental design

10 rats were used (5 males, 5 females).
No control group was used as it is documented that sesame seed oil is non toxic.
The animals were treated with a dose of 2000 mg/kg and was administered at a volume of 10 ml/kg.

Administration
The test material (10 ml/kg) was administered in one dose and applied directly on the skin.

Observations

General conditions of the animals were controlled daily for 14 days. All data relative to the study, including observations and examination were recorded and signed daily. Observations included:

Mortality
Animals were observed in the morning of every working day.

Clinical signs and behavior
Every clinical symptom, including possible variations in somotomotor activity, was daily recorded in every single animal. Clinical observations included:
- tegumentary apparatus
- mucosae conditions
- respiratory activity
- sensorium conditions

Body weight
Animals were weighed before the experiment, after 7 days and then at the end of the study.

Necropsy
At the end of the observation period rats were sacrificed and a necroptic survey was performed.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No death occurred during the study among the treated animals.

Clinical signs:

other: No clinical signs were observed during the experimental observation period.

Gross pathology:

At the ante-mortem and post-mortem examination in all animals no pathological symptoms were observed. Nothing abnormal was found in the autopsy on the animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal LD50 of the test material in the rat was found to be >2000 mg/kg bw under the conditions of the test.

Executive summary:

The test of acute dermal toxicity was performed on a group of ten rats (5 male and 5 females). The test material, COSMACOL EOI, was administered at a dose of 2000 mg/kg by dermal application. During the study the animals were observed daily for 14 days (5 out of 7) for signs of toxic symptoms. These signs were:

mortality;

evaluation of body functions;

evaluation of the tegumentary apparatus;

evaluation of mucosa conditions;

evaluation of possible variations in somatomotory activity

and sensorium conditions.

Body weight was recorded weekly.

At the end of the test autopsy was carried out on all animals.

The results obained during the study can be summarized as follows:

Mortality

During the study no case of mortality occurred.

Clinical symptoms

No clinical symptoms related to the test were observed.

Weight increase

Weight increase was normal for this species.

Necropsy findings

Animals showed no pathological symptoms.

Nothing abnormal was found in the autopsy.

DL50

The lethal dose 50 is superior 2000 mg/kg.

Under experimental conditions the test material COSMACOL Eor was found to be NON TOXIC.