Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From February 13 to March 1st, 2001
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
1996
Deviations:
yes
Remarks:
Temporary deviations from the maximum level for temperature (with a maximum of 1°C) occurred. Based on laboratory historical data these deviations were considered not to have affected the study integrity.
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
Official Journal ofthe European Communities No. L 248, 1996.
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Tris(ethyl acetoacetato-O1',O3)aluminium
EC Number:
239-343-8
EC Name:
Tris(ethyl acetoacetato-O1',O3)aluminium
Cas Number:
15306-17-9
Molecular formula:
C18H27AlO9
IUPAC Name:
Aluminum, tris(ethyl 3-oxobutanoato-O1',O3)
Test material form:
liquid: viscous

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approx. 8 weeks old.
- Weight at study initiation: body weight variation did not exceed ± 20 % of the sex mean.
- Fasting period before study: food was withheld overnight (for a maximum of 20 hours) prior to dosing until approximately 3 - 4hours after administration of the test substance.
- Housing: group housing of 3 animals per sex per cage in labelled Macrolon cages (type IV; height 15 cm.) containing purified sawdust as bedding material.
- Diet: free access to standard pelleted laboratory animal diet.
- Water: free access to tap-water.
- Acclimation period: acclimatisation period was at least 5 days before start oftreatment under laboratoryconditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21± 3 °C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours dark per day

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
Class-method, limit test
Doses:
Limit test: 2000 mg/kg (10 ml/kg) bodyweight. Single dosage on day 01.
No. of animals per sex per dose:
3 animals per sex per dose (limit test:total 6 animals).
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality and viability were observed twice daily. The time of death was recorded as precisely as possible.
- Necropsy of survivors performed: yes.The animals surviving to the end of the observation period were sacrificed by asphyxiation using a oxygen/carbon dioxide procedure. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities recorded.
- Other examinations performed: Clinical signs, body weight and macroscopic findings were analyzed during the test.
- Scoring of Clinical signs: at periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
Statistics:
No statistical analysis was performed (The method used is noti ntended to allow the calculation of a precise LD50 value).

Results and discussion

Preliminary study:
Only limit test performed.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One male was found dead on day 6. No further mortality occurred.
Clinical signs:
Hunched posture was noted in all males on day 1 and hunched posture, lethargy, piloerection, ptosis and/or chromodacryorrhoea were noted among the females during the study period.
From one female, some toes of the right front leg were missing from day 5 onwards. This finding was considered to have occurred by accident and was considered not to interfere with the purpose of the study.
Body weight:
Body weight loss and reduced body weight gain was noted among the animals during the first week post treatment. All animals regained weight during the second week.
Gross pathology:
Macroscopic post mortem examination of the male found dead on day 6 revealed abnormalities of the liver(right lateral lobe, papillary process, right median lobe many grey/white foci). No abnormalities were found at macroscopic examination of the surviving animals.

Applicant's summary and conclusion

Interpretation of results:
other: not classified for acute oral toxicity according to the CLP Regulation (EC n.1272/2008)
Conclusions:
LD50 rat oral route > 2000 mg/kg and no classification for acute oral toxicity is required according to the CLP Regulation (EC n.1272/2008).
Executive summary:

The substance was tested for acute oral toxicity according to EC Commission Directive 96/54/EC, Part5.1 tris "Acute Toxicity-Oral,Acute Toxic Class Method" and according to OECD No.423, "Acute Oral Toxicity-Acute Toxic Class Method“.

The test item was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg bodyweight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (day15).

One male was found dead on day 6. No further mortality occurred. Hunched posture was noted in all males on day 1 and hunched posture, lethargy, piloerection, ptosis and/or chromodacryorrhoea were noted among the females during the study period. Bodyweight loss and reduced body weight gain was noted among the animals during the first week post treatment. All animals regained weight during the second week. Macroscopic postmortem examination of the male found dead on day 6 revealed abnormalities of the liver (right lateral lobe, papillary process, right median lobe many grey/white foci). No abnormalities were found at macroscopic examination of the surviving animals.

The oral LD50 value of test item in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results and according to the CLP Regulation (EC n.1272/2008) no classification regarding acute oral toxicity is required for Tris(ethyl acetoacetato-O1',O3)aluminium.