Registration Dossier

Administrative data

Description of key information

The test item is not to be considered acute toxic. The LD50 is 9518 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
In the current study the narcotic potencies and lethal effetcs of aliphatic alcohols and their alkyl esters were assessed. A group of 10 - 35 male and female rabbits was treated with the test item. Administration of the test material was by stomach tube. The lethal dose (LD50) which was the quantity that caused death in 50% of the treated rabbits was also determined.
GLP compliance:
not specified
Limit test:
no
Species:
rabbit
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 1.5 - 2.5 kg
- Fasting period before study: no
- Acclimation period: 2 weeks
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
Not specified.
No. of animals per sex per dose:
10 - 35 animals in total
Control animals:
not specified
Sex:
male/female
Dose descriptor:
LD50
Effect level:
9 518 mg/kg bw
Based on:
test mat.

Based on the molecular weight of 144.21 g/mol and an LD50 value of 66 mmol/kg, an LD value of 9518 mg/kg was calculated.

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 was determined to be 9518 mg/kg.
Executive summary:

In the current study the narcotic potencies and lethal effects of aliphatic alcohols and their alkyl esters were assessed. A group of 10 - 35 male and female rabbits was treated with the test item. Administration of the test material was by stomach tube.

The lethal dose (LD50) which was the quantity that caused death in 50% of the treated rabbits was also determined.

The LD50 was determined to be 9518 mg/kg. No other details or results were provided. However, according to the CLP Regulation the test item should not be classified.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
9 518 mg/kg bw
Quality of whole database:
Even though the study is not according to OECD or GLP, the result is reliable within a weight of evidence approach. With the dermal acute and intraperitoneal acute studies and the read-across data of ehyl hexanoate it is evident that the substance is not acute toxic.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Principles of method if other than guideline:
There are no details on the study protocol. The test material was applied to the skin of 10 rabbits. Mortality and/or systemic effects were observed over a 14 day period. Gross necropsy was conducted on all animals.
GLP compliance:
not specified
Test type:
fixed dose procedure
Limit test:
yes
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No information given
Type of coverage:
not specified
Vehicle:
not specified
Duration of exposure:
Not specified.
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
10 (sex not specified)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No animals died.
Clinical signs:
There were no effects observed
Body weight:
not specified
Gross pathology:
Necropsy findings were routine and not compound-related.
Interpretation of results:
GHS criteria not met
Conclusions:
The test item is not acute dermal toxic. The LD50 is > 5000 mg/kg bw.
Executive summary:

In the current study the acute dermal toxicity of the test item was assessed in rabbits. The study was not according to OECD and GLP was not specified.

The test material was applied to the skin of 10 rabbits. Mortality and systemic effects were observed over a period of 14 days. Gross necropsy was conducted on all animals. The dose used was 5000 mg/kg bw.

No animals died during the course of the study and no specific compound-related effects were observed. Therefore, the dermal acute LD50 is > 5000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
Even though the study is not according to OECD or GLP, the result is reliable and in support of the oral acute toxicity studies to strengthen that the substance is not acute toxic.

Additional information

For acute oral toxicity 2 studies are relevant: Munch (1972) and Moreno (1975). The study by Munch assessed the oral acute toxicity of butyl butyrate. Here, narcotic potencies and lethal effetcs of aliphatic alcohols and their alkyl esters were assessed. A group of 10 - 35 male and female rabbits was treated with the test item. Administration of the test material was by stomach tube. The lethal dose (LD50) which was the quantity that caused death in 50% of the treated rabbits was also determined. The study by Moreno assessed the read-across substance ethyl hexanoate. The acute oral effects were investigated in rats by observation of the animals for a period of 2 weeks after a single dose of 5000 mg/kg.

The results indicate that the LD50 of the esters is very high:

- butyl butyrate: 9518 mg/kg bw

- ethyl hexanoate: > 5000 mg/kg bw

Even though the available studies did not use an OECD guideline to perform the test, the results indicate that both esters are not toxic after administration of a high single dose via the oral route. The studies on their own are considered not strong enough due to flaws, however, in a weight-of-evidence approach the combined data clearly indicate that butyl butyrate is not acute toxic via the oral route.

The observation that the substance is not acute toxic can be strengthened by providing data on other routes, even though this is not a REACH requirement for an Annex VII dossier.

In the study of Moreno (1977) 10 rabbits were exposed via the dermal route and observed for 14 days. No animals died during the study and no adverse effects were observed. Therefore, the dermal LD50 was > 5000 mg/kg bw. In the study Selisko (1962) rats were administered the test material via intraperitoneal injections and observed for 24 hours. The median lethal dose was determined to be 2200 mg/kg bw.

Taking together all available information it can be stated that the substance is not acute toxic and the substance does not need to be classified.

Justification for classification or non-classification

According to the CLP regulation a substance is considered acute toxic when the acute toxicity estimates (ATE) for the oral route is =< 2000 mg/kg bodyweight. The oral LD50 of the test item is 9518 mg/kg bw, the substance is not to be classified as acute toxic for the oral route.

The CLP regulation states that a substance is considered acute toxic via the dermal route when the ATE is =< 2000 mg/kg bodyweight. The dermal LD50 of the test item is 5000 mg/kg bw and so the substance is also not to be classified as acute toxic for the dermal route.

The available data is sufficient to not classify the substance as an acute toxic substance.