1,3-dimethylbut-3-enyl isobutyrate

Endpoint summary

Description of key information

Acute toxicity: oral: LD50 Combined > 5000 mg/kg bw (similar to OECD 401, rats, K, rel.2);
Acute toxicity dermal: no study available
Acute toxicity inhalation: no study available 

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:

key study

Study period:

December 06, 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was performed prior to the OECD Test Guideline No. 401 but the protocol is similar to that guidance.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

other: US FHSA CFR 1500.3 (HSLA)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

(environmental conditions not reported)

Principles of method if other than guideline:

Acute gavage administration to rats.

GLP compliance:

yes

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: Blue Spruce Farms, Inc., Altamont, NY.
- Weight at study initiation: 183-225 g
- Fasting period before study: Animals were fasted overnight (ca. 18 h) prior to oral intubation.
- Housing: Animals were housed in wire mesh bottom cages in rooms with temperature control.
- Acclimation period: ca. 2 weeks

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: no data

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: Animals were observed three times a day on the day of dosing, twice daily on Day 1 and once daily for the remainder of the study. All gross or visible toxic or pharmacological effects were recorded.
- Necropsy of survivors performed: no; all animals that died during the study were subjected to a complete gross necropsy.

Statistics:

None

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: one of ten animals died on day 2 post dosing

Mortality:

One of ten animals died on day 2 post dosing. The 95 % confidence interval for this 10 % rate of mortality is 0 to 40 % when the test material was administered to rats orally at a level of 5000 mg/kg bw.

Clinical signs:

other: - Diarrhea was observed in 3/5 females; ataxia in 4/5 male and 5/5 female animals; decreased activity in all animals

Gross pathology:

- No abnormalities were noted at necropsy except pale lungs, mottled liver, pale kidneys and small & granular spleen were observed in one male.

Other findings:

None

None

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Oral LD50 Combined > 5000 mg/kg bw

Executive summary:

In an acute oral toxicity study (limit test) performed similarly to OECD Guideline No. 401 and in compliance with GLP, groups (5/sex/dose) of Sprague-Dawley rats were given a single oral (gavage) dose of test material at 5000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and all the animals that died during the study were sacrificed for macroscopic examination.

One of ten animals died on day 2 post dosing. Diarrhea was observed in 3/5 females; ataxia in 4/5 male and 5/5 female animals; decreased activity in all animals. Surviving animals showed expected gains in bodyweight over the 14-day study period. No abnormalities were noted at necropsy except pale lungs, mottled liver, pale kidneys and small & granular spleen were observed in one male.

Oral LD50 Combined > 5000 mg/kg bw.

 

Under the test conditions, the test material is not classified for acute oral toxicity according to the annex VI of the Regulation EC No. 1272/2008 (CLP).

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Quality of whole database:

The key study is non-GLP compliant but of good quality (Klimisch score = 2)

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

Acute toxicity: oral

A key study was available (FDRL 1979, Rel.2). This acute oral toxicity study was performed prior to the OECD test guideline No. 401 but the protocol is similar to that guidance. Groups of rats (5/sex/dose) were administered a single oral (gavage) dose of test material at 5000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and all the animals that died during the study were sacrificed for macroscopic examination.

One of ten animals died on day 2 post dosing. Diarrhea was observed in 3/5 females; ataxia in 4/5 male and 5/5 female animals; decreased activity in all animals. Surviving animals showed expected gains in bodyweight over the 14-day study period. No abnormalities were noted at necropsy except pale lungs, mottled liver, pale kidneys and small & granular spleen were observed in one male.

Oral LD50 Combined > 5000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
Only one study available

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008 including ATP7.

Self classification:

Acute toxicity via Oral route:

Based on the available data, the substance is not classified according to the Regulation (EC) No. 1272/2008 as the LD50 is greater than 5000 mg/kg bw.

Acute toxicity via Dermal route:

No data was available.

Acute toxicity (Inhalation):

No data was available.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the Annex VI of the Regulation (EC) No. 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no significant health effects were observed immediately or delayed after exposure at the guidance value (oral) for a Category 1 classification (C ≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw ≥ C > 300 mg/kg bw). No classification is required.

Specific target organ toxicity: single exposure (Dermal):

No data was available.

Specific target organ toxicity: single exposure (Inhalation):

No data was available.