Registration Dossier

Administrative data

Description of key information

The test item is not acute oral toxic as the LD50 is > 3371.5 mg/kg bw.

This LD50 is determined in a read-across approach by taking into account the difference in molecular weight between the source substance (3-methylbutyl isovalerate) and the target substance (ethyl isobutyrate).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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:
Read-across from 3-methylbutyl isovalerate to ethyl isobutyrate is considered justified based on strong similarities with regard to chemical structure and metabolic pathways. A full read-across justification including comparison of toxicological profiles will be included in section 13 of the IUCLID dossier.
Reason / purpose:
read-across source
Sex:
female
Dose descriptor:
LD50
Effect level:
> 3 371.5 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Corrected for MW
Interpretation of results:
GHS criteria not met
Conclusions:
Read-across was done from 3-methylbutyl isovalerate. Based on the result, and on the structural, chemical and toxicological similarities between 3-methylbutyl isovalerate and ethyl isobutyrate, the LD50 for ethyl isobutyrate was calculated to be > 3371.5 mg/kg bw.
Executive summary:

Read-across was done from 3-methylbutyl isovalerate. The purpose of the current study was to assess the potential toxicity of 3-methylbutyl isovalerate after a single oral administration. Acute oral dosing was performed according to OECD 423 and GLP.

Female Sprague-Dawley rats were allocated to groups at random. 1 animal was assigned to one group for the Step 1 and two animals were assigned to another group for Step 2. The animals of both dose groups (Steps 1 and 2) received 5000 mg/kg of 3-methylbutyl isovalerate. All animals were monitored for clinical signs and body weight changes during the 14 day observation period after administration. They were subjected to gross necropsy at the end of the observation period.

No animals died during the study and thus there were no effects on the mortality.

In 1 animal mucous stool was observed on day 1 after dosing, however, it disappeared on day 2 after dosing.

Regarding the body weights of the animals, a tendency to suppress body weight gain was observed in all animals on day 1, however, it returned to normal on day 3. This change was considered to be a test substance-related effect.

During necropsy no grossly visible evidence of morphological abnormalities were observed in any animal.

Based on the result of the acute oral toxicity study in Sprague-Dawley rats, 3-methylbutyl isovalerate is not classified for acute oral toxicity and the LD50 > 5000 mg/kg bw.

Based on the result, and on the structural, chemical and toxicological similarities between 3-methylbutyl isovalerate and ethyl isobutyrate, the LD50 for ethyl isobutyrate was calculated to be > 3371.5 mg/kg bw. This LD50 value is calculated from the LD50 of the source substance 3 -methylbutyl isovalerate by taking into account the difference in molecular weight between source and target substance.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
3 371.5 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

For the acute oral toxicity endpoint there are 2 studies available that can be used for ethyl isobutyrate.

In the key study on the read-across substance 3-methylbutyl isovalerate the potential toxicity of 3-methylbutyl isovalerate was evaluated after a single oral administration according to OECD 423 and GLP, using female Sprague-Dawley rats. The dose was 5000 mg/kg and all animals were monitored for clinical signs and body weight changes for 14 days and were subjected to gross necropsy at the end of the observation period. No animals died during the study and no gross morphological abnormalities were observed in any animal. There was a tendency to suppress body weight gain in all animals on day 1, however, this returned to normal on day 3. Based on the result of the acute oral toxicity study in Sprague-Dawley rats, the LD50 for 3-methylbutyl isovalerate was > 5,000 mg/kg bw.

Based on the result, and on the structural, chemical and toxicological similarities between 3-methylbutyl isovalerate and ethyl isobutyrate, the LD50 for ethyl isobutyrate was calculated to be > 3371.5 mg/kg bw. This calculation takes into account the difference in molecular weight between the source and target substance.

In the supporting study ethyl isobutyrate was tested for acute oral toxicity, however, the method of testing was not described in detail. The only available information is that 10 rats were dosed 1 time with 5000 mg/kg bw of the test item and observed for 14 days. No animals died and no symptoms were noted. The LD50 was determined to be > 5000 mg/kg.

Taken together, the LD50 for ethyl isobutyrate is > 3371.5 mg/kg bw. This value is calculated from the LD50 of the source substance, taking into account the difference in molecular weight between source and target substance.

Justification for classification or non-classification

According to the EU Regulation No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures (CLP) the substance is not considered to be classified as acute toxic. The LD50 is > 3371.5 mg/kg bw, which is above the cut-off value of 2000 mg/kg bw. This value was calculated based on a read-across study. Additionally, a supporting study on the target substance itself indicates that the substance is not toxic at 5000 mg/kg bw in an acute oral study. Taken together, the substance should not be classified.