D-Glucitol, 1,3:2,4-bis-O-[(4-chlorophenyl)methylene]-

Acute Toxicity: oral

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

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. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(1R)-1-[(4R,4aR,8aS)-2,6-bis(4-chlorophenyl)-hexahydro-[1,3]dioxino[5,4-d][1,3]dioxin-4-yl]ethane-1,2-diol

EC Number:

700-591-1

Cas Number:

82203-23-4

Molecular formula:

C20H20Cl2O6

IUPAC Name:

(1R)-1-[(4R,4aR,8aS)-2,6-bis(4-chlorophenyl)-hexahydro-[1,3]dioxino[5,4-d][1,3]dioxin-4-yl]ethane-1,2-diol

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 or test system 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:

other: No clinical signs related to the administration of the test item were observed.

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.