Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
March/April 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP-compliant guideline study with the following deviations: - According to the guideline, healthy young adults should be used. The age of the rats was missing in this report. - The analytical purity of the test substance is not indicated in the report.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
EC number: 241-234-5
No further significant information on test material was stated.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. A. Ivanovas, 7964 Kisslegg/Allgäu
- Age at study initiation: Not reported
- Weight at study initiation: Males: 105-130 g; Females: 95-130 g
- Housing: Group housing of five animals per sex per cage in labelled Makrolon cages (type III) containing sawdust bedding material (Fa. Brandenburg, 2849 Goldenstedt-Arkeburg).
- Diet (ad libitum except overnight prior to and approx. 4 hours after dosing): Pelleted rodent diet (Ssniff R10 pellets, Ssniff Versuchstierdiäten, 4770 Soest/Westf.
- Water (ad libitum): Tap water
- Acclimation period: 5 days before start of treatment

ENVIRONMENTAL CONDITIONS
Animals were housed in a controlled environment.
- Temperature: ca. 20°C
- Relative humidity: 40 - 60 %
- Air changes: Approx. 10 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 1%

MAXIMUM DOSE VOLUME APPLIED: 5.0 ml/kg
The control animals received the vehicle alone.
Doses:
Control (group I), 261 mg/kg (group II), 316 mg/kg (group III), 383 mg/kg (group IV), 464 mg/kg (group V), 562 mg/kg (group VI), 681 mg/kg (group VII)
No. of animals per sex per dose:
5 male / 5 female
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: On the day of dosing animals were observed for signs of reaction to treatment at frequent intervals. On subsequent days animals were observed at leaste once daily. Individual bodyweights were recorded on the day of dosing and on days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
The acute oral median lethal dose (LD50) based on the mortality rate (x/n) during 14 days after dosing was calculated using the method of Finney, I.J. (1971) Probit Analysis (3rd edition) Cambridge University Press.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
333 mg/kg bw
Based on:
test mat.
95% CL:
> 188 - < 417
Mortality:
Number of dead males per dose:
Control: 0/5
261 mg/kg: 0/5
316 mg/kg: 4/5 (within 6 hours after dosing)
383 mg/kg: 3/5 (within 24 hours after dosing)
464 mg/kg: 4/5 (within 24 hours after dosing)
562 mg/kg: 5/5 (within 6 hours after dosing)
681 mg/kg: 5/5 (within 6 hours after dosing)

Number of dead females per dose:
Control: 0/5
261 mg/kg: 0/5
316 mg/kg: 4/5 (within 6 hours after dosing)
383 mg/kg: 3/5 (within 24 hours after dosing)
464 mg/kg: 4/5 (within 6 hours after dosing)
562 mg/kg: 5/5 (within 24 hours after dosing)
681 mg/kg: 5/5 (within 6 hours after dosing)
Clinical signs:
Slight pilo-erection and hunched posture was observed in the control animals on the day of dosing. Clinical signs observed in rats treated with barium hydroxide included pilo-erection, hunched posture, pallor of extremities, abnormal gait (waddling), increased respiratory rate, decreased respiratory rate, gasping or laboured respiration, diarrhoea, decreased motility, loss of righting reflex and muscular spasms. Loss of coordination was observed in one female at 383 mg/kg and one other female at 562 mg/kg. Straubtail was seen in one male at 316 mg/kg.
Recovery of the survivors was complete by day 2 in rats at 261 mg/kg and 316 mg/kg, by day 3 in rats at 383 mg/kg and by day 4 in rats at 464 mg/kg as judged by external appearance and behaviour.
Body weight:
A depressed bodyweight gain was observed in the surviving male rat of group III (316 mg/kg) during the first and second week and in one surviving female rat of group IV (383 mg/kg) during the first week. Poor bodyweight gain was also observed in the surviving male rat of group V (464 mg/kg).
Gross pathology:
Autopsy mainly revealed congestion of liver and spleen. Congestion and haemorrhaging was seen in the mucous membrane of the stomach.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
An LD50 of 333 mg/kg bw has been calculated for males/females for barium hydroxide. No difference in sensitivity was observed between males and females. According to the test result the substance has to be classified as harmful if swallowed (H302).

Executive summary:

In a GLP compliant acute oral toxicity study, performed according to OECD guideline 401, the test item Barium hydroxide was administered to groups of 5 male and 5 female Sprague Dawley rats at dose levels of 261, 316, 383, 464, 562 and 681 mg/kg body weight. Mortalities occurred within 24 hours after dosing. No difference in sensitivity was observed between males and females. Signs of reaction to treatment included pilo-erection, hunched posture, pallor of extremities, abnormal gait (waddling), increased or decreased respiratory rate, gasping or laboured respiration, diarrhoea, decreased motility, loss of righting reflex, muscular spasms and loss of coordination. Complete recovery was evident in surviving animals by day 4 as judged by external appearance and behaviour. Autopsy mainly revealed congestion of liver and spleen. Congestion and haemorrhaging in the mucous membrane of the stomach was also observed. Body weight gain was poor in the surviving animals of the 316, 383 and 464 mg/kg groups.

In conclusion, the LD50 of Barium hydroxide is calculated to be 333 mg/kg body weight by oral route in the rat.