Registration Dossier

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method

Test material

Constituent 1
Chemical structure
Reference substance name:
Dilithium tetraborate
EC Number:
234-514-3
EC Name:
Dilithium tetraborate
Cas Number:
12007-60-2
Molecular formula:
B4Li2O7
IUPAC Name:
dilithium(1+) bicyclo[3.3.1]tetraboroxane-3,7-bis(olate)
Test material form:
solid: bulk
Specific details on test material used for the study:
Test item storage: At room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Sex: 9 Females (nulliparous and non-pregnant). Each dose group consisted of 3 animals.
- Age at study initiation: Young adult animals (approximately 10-11 weeks old) were selected.
- Weight at study initiation: 165 to 200 g.
- Housing: polycarbonate cages (Makrolon MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles.
- Diet: Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) was provided ad libitum
- Water: Municipal tap-water was freely available
- Acclimation period: At least 5 days before dosing.
- Animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item.

ENVIRONMENTAL CONDITIONS
- 18 to 24°C with a relative target humidity of 40 to 70%

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: medicinal white oil
Details on oral exposure:
VEHICLE
- Identification: MOL WO M46 medicinal white oil
- Justification for choice of vehicle: The vehicle was selected based on information provided by the Sponsor
- Lot/batch no. (if required): 208885/A
- Specific gravity: 0.833-0.893 g/cm3 (at 15°C)

A dose volume of 10 mL/kg body weight was used for each dose.

The oral route was selected as it is a possible route of human exposure during manufacture, handling or use of the test item.

The dose levels were based on the OECD test guidelines and were selected from the series 5 (lowest dose level), 50, 300 and 2000 (highest dose level) mg/kg body weight.
Doses:
The first group was treated at a dose level of 2000 mg/kg. Based on the results, two additional groups were dosed at 300 mg/kg.
No. of animals per sex per dose:
3 Females per dose group.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day. Postdoes observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. All the animals were examined for reaction to dosing and the onset,intensity and duration of these signs were recorded.
- All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities were recorded.
- The body weights of the animals were recorded individually on Day 1 (predose), 8 and 15.

Results and discussion

Preliminary study:
Not applicable
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
500 mg/kg bw
Based on:
test mat.
Mortality:
At 2000 mg/kg, all animals were found dead on Day 2. At 300 mg/kg, no mortality occurred.
Clinical signs:
Hunched posture, uncoordinated movements, piloerection and ptosis were noted for all animals on Day 1 at 2000 mg/kg. At 300 mg/kg, hunched posture, uncoordinated movements and piloerection were noted for all animals between Days 1 and 2.
Body weight:
The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected for normal, untreated animals of the same age and strain.
Gross pathology:
Abnormalities of the stomach (gelatinous contents and/or dark red/discoloured/thickened glandular mucosa) were found in the animals that died during the study, at macroscopic post mortem examination. Macroscopic post mortem examination of the surviving animals at termination did not reveal any abnormalities.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The oral LD50 value of dilithium tetraborate in Wistar rats was established to be within the range of 300-2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 500 mg/kg body weight.
Executive summary:

The potential toxicity of dilithium tetraborate was investigated by administration of a single dose of the test substance by oral gavage to female rats according to OECD 423. Initially, Dilithium tetraborate was administered by oral gavage to three female Wistar rats at 2000 mg/kg body weight.  At 2000 mg/kg, all animals were found dead on Day 2. Two additional groups were dosed at 300 mg/kg body weight. At this dose level, no mortalities were observed but effects including hunched posture, uncoordinated movements and piloerection were noted for all animals between Days 1 and 2. For both dose levels, the body weight gain of the surviving animals was shown to be normal over the study period.

The oral LD50 value of dilithium tetraborate in Wistar rats was therefore established to be within the range of 300-2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 500 mg/kg body weight.