Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
29 January 2013-21 February 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

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
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): barium nitrate
- Substance type: white crystals
- Physical state: solid
- Analytical purity: 99.52 %
- Lot/batch No.: 120724
- Expiration date of the lot/batch: 2013-09-13
- Stability under test conditions: stable
- Storage condition of test material: Room temperature in the dark

Test animals

Species:
rat
Strain:
other: Wistar strain Crl:WI (Han) (outbred, SPF-Quality).
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: approx. 10 weeks old
- Weight at study initiation: 146-181g .Body weight variation did not exceed +/- 20% of the sex mean
- Fasting period before study: Overnight prior to dosing and until 3-4 hours after administration of the test substance.
- Housing: Group- 3 animals per cage- labeled Makrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
- Diet (e.g. ad libitum): Ad libitum-pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water (e.g. ad libitum): Ad libitum tap water.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C
- Humidity (%): 40 to 70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle

IN-LIFE DATES: From: 29 January 2013 To: 21 February 2013

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: varied depending on body weight
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: Selected based on trial formulations performed at WIL Research Europe and on test substance data supplied by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 10mL/kg

DOSAGE PREPARATION (if unusual):To obtain homogeneity, the formulations were heated up to maximally 70 ºC for maximally 30 minutes. The formulations were allowed to cool down to maximally 40 ºC prior to dosing.

CLASS METHOD (if applicable): yes.
The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 2000 mg/kg. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.


Doses:
2000 mg/kg (10 mL/kg) body weight.
300 mg/kg (10 mL/kg) body weight.
50 mg/kg (10 mL/kg) body weight.
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. Body weights recorded at Day 1 and Day 15 (or death).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 50 - < 300 mg/kg bw
Based on:
test mat.
Mortality:
The three animals dosed at 2000 mg/kg were found dead within 2 hours post-dose. Two (of the three) animals dosed at 300 mg/kg were found dead on Days 1 or 3. No mortality occurred at 50 mg/kg.
Clinical signs:
At 2000 mg/kg no clinical signs were noted.
At 300 mg/kg hunched posture, flat posture, lethargy, piloerection, uncoordinated movements, labored respiration, slow breathing were noted.
At 50 mg/kg hunched posture, piloerection, uncoordinated movements, chromodacryorrhoea were noted.
The surviving animals recovered from the symptoms between Days 2 and 3.
Body weight:
The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
Animals that were found dead had of the jejunum (several reddish foci) in one animal dosed at 2000 mg/kg and abnormalities of the stomach (several dark red foci at the glandular mucosa) and thymus (many dark red foci) in one animal dosed at 300 mg/kg. No test substance related macroscopic abnormalities were seen in the remaining animals found dead or in any of the surviving animals.

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The oral LD50 value of barium nitrate in rats was found to be in the range of 50-300 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 300 mg/kg body weight. This value is used for risk assessment purposes.

Based on these results and according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011), Barium Nitrate should be classified as: Toxic if swallowed (Category 3) for acute toxicity by the oral route. According to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures, barium nitrate should be classified as Category 3 and should be labeled as H301: Toxic if swallowed.