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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Trimethylacetic anhydride
EC Number:
216-263-1
EC Name:
Trimethylacetic anhydride
Cas Number:
1538-75-6
Molecular formula:
C10H18O3
IUPAC Name:
2,2-dimethylpropanoic anhydride
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Crl:WI (HAN)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Females: nulliparous and non-pregnant
- Age at study initiation: no data available
- Weight at study initiation: 158 - 183 g
- Fasting period before study: no data available
- Housing: 3 animals per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 55 +/- 5 %
- Air changes (per hr): >10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: corn oil + 10% acetone (dried with molecular sieve)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 5 mg/ml and 200 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: analytically determined stability in the formulation

CLASS METHOD
- Rationale for the selection of the starting dose: limit test
Doses:
2000 mg/kg bw - 300 mg/kg bw
No. of animals per sex per dose:
3 (2000 mg/kg bw), 3 + 3 (300 mg/kg bw)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation (30 min after dosing, periodically during the first 24 hours after dosing, thereafter at least once daily); weighing [weekly (animals of dose group 2000 mg/kg bw were additionally weight on day 3 before prematurely sacrificed]
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, gross pathology
Statistics:
not applicable

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Based on clinical signs (see below) and a body weight reduction all animals of the 2000 mg/kg body weight dose group were prematurely sacrificed on day 3 of the study. No mortality was observed in animals dosed with 300 mg/kg bw.
Clinical signs:
In animals dosed with 2000 mg/kg b.w. piloerection, decreased motility, high legged gait, uncoordinated gait, red incrusted eye lids (only one animal) and narrowed palpebral fissures were observed. No clinical signs were observed in animals dosed with 300 mg/kg body weight.
Body weight:
In all animals dosed with 2000 mg/kg b.w. a reduction of body weight (by 5.9, 8.7 and 8.9%) was observed until day 3 of the study. There were no toxicologically significant effects on body weight development in animals dosed with 300 mg/kg body weight.
Gross pathology:
In all animals of the 2000 mg/kg dose group the caecum was diminished in size. Additionally, stomachs were complete filled up with feed (2/3 animals) and a solid change of content (2/3 animals) of the caecum were observed at day 3 of the study. At the end of the study period in two animals treated with 300 mg/kg pale kidneys were detected.

Applicant's summary and conclusion

Executive summary:

According to OECD guideline 423 the LD50 cut-off is 500 mg/kg b.w .. In animals dosed with 2000 mg/kg b.w. of the test substance piloerection, decreased motility, high legged gait, uncoordinated gait, red incrusted eye lids and narrowed palpebral fissures were observed. In all animals dosed with 2000 mg/kg b.w. a reduction of body weight was observed until day 3 ofthe study. Based on these results all animals of the 2000 mg/kg body weight dose group were prematurely sacrificed on day 3 of the study. In all animals of the 2000 mg/kg dose group the caecum was diminished in size. Additionally, in two animals the stomachs were completely filled up with feed and a solid change of content of the caecum were observed at necropsy on day 3 of the study. A dose of 300 mg/kg body weight was tolerated by female rats without mortalities, clinical signs and effects on body weight development. At the end of the study period in two animals treated with 300 mg/kg pale kidneys were detected.