Barium tartrate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November 20, 2014 - December 18, 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(2001)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

(2008)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

(2002)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Barium tartrate

EC Number:

227-615-9

EC Name:

Barium tartrate

Cas Number:

5908-81-6

Molecular formula:

C4H4O6Ba

IUPAC Name:

Barium L(+)-(2R,3R)-tartrate

Details on test material:

- Name of test material (as cited in study report): Barium tartrate
- Appearance: White powder

Test animals

Species:

rat

Strain:

other: Crl:WI (Han)

Sex:

female

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 10-11 weeks old)
- Weight at study initiation: 178-192 g (1st group), 184-207 g (2nd group) and 178-184 g (3rd group)
- Fasting period before study: Animals were deprived of food overnight prior to dosing
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water: Free access to tap water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 – 24
- Humidity (%): 40 - 70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: November 20, 2014 To: December 18, 2014

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

GAVAGE METHOD: plastic feeding tubes.

Frequency: single dosage, on Day 1.

VEHICLE
- The vehicle was selected based on trial formulations performed at WIL Research Europe and on test substance data supplied by the sponsor.

DOSE VOLUME APPLIED:
2000 mg/kg (10 mL/kg) body weight
300 mg/kg (10 mL/kg) body weight

DOSAGE PREPARATION
The formulations (w/v) were kept at room temperature and were dosed within 4 hours after adding the vehicle to the test substance. Homogeneity was obtained to visually acceptable levels. No correction was made for purity of the test substance.

Doses:

- 2000 mg/kg body weight (1 group)
- 300 mg/kg body weight (2 groups)

No. of animals per sex per dose:

9 (3 groups of three females in a stepwise manner)

Control animals:

no

Details on study design:

Animals were deprived of food until 3-4 hours after administration of the test substance.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily. Animals showing pain, distress or discomfort, which was considered not transient in nature or was likely to become more severe, were sacrificed for humane reasons based on OECD guidance document on humane endpoints (ENV/JM/MONO/ 2000/7). The time of death was recorded as precisely as possible.
Body weights: Days 1 (pre-administration), 8 and 15 and at death (if found dead or sacrificed after Day 1)
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: All animals were subjected to necropsy and descriptions of all internal macroscopic abnormalities recorded.
- Other examinations performed: none

Statistics:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

- At 2000 mg/kg bw, one animal was sacrificed for humane reasons on Day 2 and one animal was found dead on Day 2
- At 300 mg/kg bw, no mortality occurred

Clinical signs:

other: - At 2000 mg/kg bw, hunched posture was noted for all animals on Days 1 and/or 2. Additionally, lethargy, uncoordinated movements, piloerection and hypothermia were also noted for the animal sacrificed for humane reasons, on Days 1 and/or 2. - At 300 mg/k

Gross pathology:

At 2000 mg/kg bw, abnormalities of the stomach (glandular mucosa: many dark red focus/foci) were found in the animal sacrificed for humane reasons.

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In an acute oral toxicity study with Barium tartrate in rats, performed according to OECD/EC test guidelines, an LD50 of > 300 - < 2000 mg/kg bw was determined. Based on this result, the substance needs to be classified for acute toxicity by the oral route (Category 4) with Harmful if swallowed (H302).

Executive summary:

The acute oral toxicity of Barium tartrate was determined in accordance with OECD 423 (2001) and according to GLP principles. The substance was administered by oral gavage to three subsequent groups of three female Wistar rats at 2000 and 300 mg/kg body weight. At 2000 mg/kg bw, one of the three animals was sacrificed for humane reasons on Day 2 and one animal was found dead on Day 2. At 300 mg/kg bw, no mortality occurred. At 2000 mg/kg bw, hunched posture was noted for all animals on Days 1 and/or 2. Additionally, lethargy, uncoordinated movements, piloerection and hypothermia were also noted for the animal sacrificed for humane reasons, on Days 1 and/or 2. At 300 mg/kg, hunched posture and piloerection were noted for all animals on Days 1, 2 and/or 3. Necropsy of the animal that was sacrificed for human reasons revealed abnormalities of the stomach. The acute oral toxicity (LD50) was determined to be > 300 - < 2000 mg/kg bw. Based on this result, the substance needs to be classified for acute toxicity by the oral route (Category 4) with Harmful if swallowed (H302).