(ethyl 3-oxobutyrato-O1',O3)bis(propan-2-olato)aluminium

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

3 to 18 October 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

The acute oral toxicity study was undertaken as a bridging study to demonstrate equivalence between the Target substance (XP 475) and the Source substance (XP 338; CAS 569318-35-0) for the read-across of other data. A full discussion of read-across and supporting data is given in the attached justification.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

27 November 2003 to 16 December 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

17 Dec 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

The substance is the Source of the read-across for other toxicological endpoints. The acute oral toxicity study shows equivalent results to the Target Substance.

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Route of administration:

oral: gavage

Vehicle:

arachis oil

Doses:

2000 mg/kg

No. of animals per sex per dose:

6

Control animals:

no

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Based on:

test mat.

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 > 2500 mg/kg.

Cross-reference 2

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Qualifier:

no guideline available

GLP compliance:

not specified

Specific details on test material used for the study:

Test material is a hydrolysis product of the test material XP 475.

Species:

rat

Route of administration:

oral: gavage

Sex:

not specified

Dose descriptor:

LD50

Effect level:

4 710 - 5 840

Based on:

test mat.

Interpretation of results:

GHS criteria not met

Conclusions:

Isopropanol LD50 range = 4710 - 5840 mg/kg. Isopropanol is a hydrolysis product of the test material XP 475. The data is provided as supporting material for the assessment of XP 475.

Cross-reference 3

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Specific details on test material used for the study:

Test material is a hydrolysis product of XP 475.

Species:

rat

Route of administration:

oral: gavage

Dose descriptor:

LD50

Effect level:

> 3 980 mg/kg bw

Based on:

test mat.

Mortality:

In rats, oral LD50 values of 3,980 mg/kg bw and higher (12,300 mg/kg bw
for males and 10,800 mg/kg bw for females) are reported. In a test with 5 male and 5 female rats
per dose, rats dosed 2-4 g/kg bw exhibited moderate diarrhea, rats dosed 8 g/kg bw showed
moderate to severe diarrhea. Doses of 10 g/kg bw killed 1/5 male and 2/5 female rats (clinical
signs: rapid erratic respiration, lethargy, severe diarrhea, ruffled and unkempt coats). After
forced feeding of 16 g/kg bw all rats died within 30 min.

Interpretation of results:

GHS criteria not met

Conclusions:

Ethyl acetoacetate, a hydrolysis product of XP 475, does not meet the criteria for classification.

Cross-reference 4

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Specific details on test material used for the study:

Test substance is a hydrolysis product of target substance.

Species:

rat

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

GHS criteria not met

Conclusions:

Aluminium hydroxide: LD50 (rat) > 5000 mg/kg.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

17th December 2001

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:

(ethyl 3-oxobutyrato-O1',O3)bis(propan-2-olato)aluminium

EC Number:

238-851-7

EC Name:

(ethyl 3-oxobutyrato-O1',O3)bis(propan-2-olato)aluminium

Cas Number:

14782-75-3

Molecular formula:

C12 H23 O5

IUPAC Name:

(ethyl 3-oxobutyrato-O1',O3)bis(propan-2-olato)aluminium

Test material form:

liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Female, nulliparous and non pregnant animals.
Age of animals: Young adult rat, 8-9 weeks old in sighting and in main study.
Body weight in sighting study: 191 g.
Body weight range in main study: 193 - 214 g.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other:

Remarks:

The test item was dosed as a formulation in Helianthi annui oleum raffinatum solution.

Details on oral exposure:

A single oral administration - followed by a fourteen-day observation period - was performed by gavage.

Doses:

Starting dose of the sighting study was selected on the OECD Guideline No.:420. A sighting study starting dose of 2000 mg/kg followed by dosing of a further four animals at this level as a limit test for relevant guideline.

No. of animals per sex per dose:

Starting dose of the sighting study was selected on the OECD Guideline No.:420. A sighting study starting dose of 2000 mg/kg followed by dosing of a further four animals at this level as a limit test for relevant guideline.

Control animals:

yes

Details on study design:

Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out 14th day after the treatment.

Results and discussion

Preliminary study:

No lethality was noted at after a single oral dose of 2000 mg/kg bw.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

The rat (No.: 7548) dosed at 2000 mg/kg bw XP 475 did not die in sighting study.
No deaths occurred at the 2000 mg/kg single oral dose of the test item in the main study. All rats survived until the end of the 14-day observation period.

Clinical signs:

No treatment related symptoms were observed in the 2000 mg/kg bw dose group throughout the 14-day post-treatment period.

Body weight:

The mean body weight of animals treated with 2000 mg/kg bw dose corresponded to their species and age throughout the study.

Gross pathology:

All animals treated with 2000 mg/kg bw of the test item survived until the scheduled necropsy on Day 14.
Slight hydrometra was observed in female No.: 7548 and severe hydrometra was detected in animal No.: 7551, respectively. Hydrometra is physiological finding and connected to the oestrus cycle of the animal. No pathological changes were found related to the effect of the test item during the macroscopic examination of animals treated with 2000 mg/kg bw of the test item.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 >2000 mg/kg.