Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011-12-27 - 2012-03-15
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Principles of method if other than guideline:
None
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): (1R)-1-[(4R,4aR,8aS)-2,6-bis(4-chlorophenyl)tetrahydro[1,3]dioxino[5,4-d][1,3]dioxin-4-yl]ethane-1,2-diol
- Physical state: white powder
- Expiration date of the lot/batch: December 2012
- Storage condition of test material: room temperature, hygroscopic

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 weeks
- Weight at study initiation: between 187 g and 206 g
- Fasting period before study: Food was removed at D-1 and then redistributed 4 hours after the test item administration
- Diet (e.g. ad libitum): foodstuff (M20, SDS) was supplied freely
- Water (e.g. ad libitum): Drinking water (tap-water from public distribution system) was supplied freely. Microbiological and chemical analyses of the water were carried out once every six months.
- Acclimation: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19°C - 25°C
- Humidity (%): relative humidity 30-70%
- Air changes (per hr): Air-conditioned with approx. 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hour light (07.00 to 19.00)/12 h dark

Administration / exposure

Route of administration:
other: suitable syringe graduated fitted with an oesophageal metal canula
Vehicle:
DMSO
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Step 1: 3 female rats
Step 2: 3 female rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Systematic examinations were carried out to identify any behavioural or toxic effects on the major physiological functions during 14 days following the administration of the test item. This examination focuses particularly on a list of symptoms, recorded as "present" or "absent" and observations were compared to historical control data. Observations and a mortality report were then carried out every day for 14 days. The animals were weighed on day D0 (just before administering the test item) then on D2, D7, and D14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopical examination

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: In accordance with the OECD guideline No. 423, the LD50 cut-off of the test item may be considered to be higher than 5000 mg/kg body weight by oral route in the rat.
Mortality:
No mortality occurred during the study.
Clinical signs:
No clinical signs related to the administration of the test item were observed.
Body weight:
The body weight evolution of the animals remained normal throughout the study.
Gross pathology:
The macroscopical examination of the animals at the end of the study did not reveal treatment related changes.

Applicant's summary and conclusion

Interpretation of results:
other: EU-GHS criteria not met
Conclusions:
No mortality occurred during the study, no clinical signs related to the administration of the test item were observed, the body weight evolution of the animals remained normal throughout the study and the macroscopical examination of the animals at the end of the study did not reveal treatment related changes.
The LD50 of the test item is higher than 2000 mg/kg body weight by oral route in the rat. In accordance with the OECD guideline No. 423, the LD50 cut-off of the test item may be considered to be higher than 5000 mg/kg body weight by oral route in the rat.