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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08-03-2017 to 29-03-2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report date:
2018

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
17 Dec 2001
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
(ethyl acetoacetato-O1',O3)(pentane-2,4-dionato-O,O')[propane-1,3-diolato(2-)-O,O']titanium
EC Number:
279-899-9
EC Name:
(ethyl acetoacetato-O1',O3)(pentane-2,4-dionato-O,O')[propane-1,3-diolato(2-)-O,O']titanium
Cas Number:
82089-64-3
Molecular formula:
C14H22O7Ti
IUPAC Name:
13-ethoxy-8,10,15-trimethyl-1λ³,5λ³-dioxa-7λ³,11λ³,12,16-tetraoxa-6-titanaspiro[5.5⁶.5⁶]hexadeca-7,10-diene-6,6,6,6-tetrakis(ylium)-1,5,9,14-tetraide
Test material form:
liquid: viscous

Test animals

Species:
rat
Strain:
Wistar
Remarks:
RccHan:WIST
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS Limited, UK
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 163 - 185g (main study)
- Fasting period before study: overnight fast immediately before and approx. 3 -4 hours after dosing
- Housing: in groups of up to four in suspended solid-floor polypropylene cages with woodflakes
- Diet: free access to food (2014C Teklad Global Rodent diet)
- Water: free access to main drinking water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25°C
- Humidity (%): 30 - 70%
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
DMSO
Doses:
300 mg/kg
2000 mg/kg
No. of animals per sex per dose:
2000 mg/kg: 1 animal (sighting study)
300 mg/kg: 1 animal (sighting study)
300 mg/kg: 5 animals
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Morbidity and mortality checks twice daily, once daily at weekend and public holidays; weighing on days 0, 7 and 14 d or at death
- Necropsy of survivors performed: yes
- Clinical observations: 30 min, 1, 2, 4 h afer dosing, then daily up to 14 d

Results and discussion

Preliminary study:
Sighting study: In the absence of toxicity at a dose level of 300 mg/kg tested in one animal, an additional animal was treated with 2000 mg/kg. At this dose level, the signs of systemic toxicity noted were hunched posture, lethargy, noisy and labored respiration, pilo-erection and dehydration. The tested animal was killed for humane reasons, 1 day after dosing.
Due to mortality and signs of systemic toxicity in the "main test" a group of five animals was tested with 300 mg/kg.

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Dose level - 2000 mg/kg (sighting study): the animal was killed 1 day after dosing, due to the occurrence of clinical signs of toxicity that were considered likely to exceed the severity limit.
Dose level - 300 mg/kg: no death
Clinical signs:
other: Dose level - 2000 mg/kg (sighting study): Signs of systemic toxicity noted were hunched posture, lethargy, noisy and labored restiration, pilo-erection and dehydration Dose level - 300 mg/kg: No signs of systemic toxicity noted during the observation peri
Gross pathology:
Necropsy:
Dose level - 2000 mg/kg (sighting study): Gaseous stomach and test item present in the stomach
Dose level - 300 mg/kg: No abnormalities

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg body weight (CLP - Category 4).
Executive summary:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg body weight (CLP - Category 4).