Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1998-03-09 to 1999-06-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Performed per OECD Guideline 401, Acute Oral Toxicity and GLP.
Cross-reference
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
Disodium wolframate
EC Number:
236-743-4
EC Name:
Disodium wolframate
Cas Number:
13472-45-2
Molecular formula:
Na2WO4
IUPAC Name:
disodium dioxotungstenbis(olate)
Details on test material:
- Name of test material (as cited in study report): Sodium Tungstate Dihydrate
- Physical state: White powder
- Analytical purity:99.9%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon, England.
- Age at study initiation: 4 to 7 wks
- Weight at study initiation: 87 to 125 g
- Fasting period before study: Overnight
- Housing: In groups of 5 rats of the same sex in metal cages with wire mesh floors.
- Diet: ad libitum- standard laboratory rodent diet (Special Diet Services RM1(E) SQC expanded pellet)
- Water: ad libitum
- Acclimation period:5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 22.5 C
- Humidity (%): 29 to 59 %
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: March 9, 1998 To: April 14, 1998

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 800, 1260, and 2000 mg/kg Bodyweight


Doses:
Animals were exposed at a fixed dose volume of 10 mL/kg bodyweight.
800 mg/kg (dose concentration 8 mg/mL).
1260 mg/kg (dose concentration of 12.6 mg/mL)
2000 mg/kg (dose concentration of 20 mg/mL).
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Mortalities: Cages of rats were checked at least twice daily for mortalities.
- Clinical signs: Animlas were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, surviving animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The nature of the clinical signs and time were recorded at each observation. All animals that survived treatment were observed for 14 days after dosing.
- Body weights: Body weights of each rat was recorded on Days 1 (prior to dosing), 8 and 15 or at death. Individual weekly body weight changes and group mean body weights were calculated.
- Necropsy of survivors performed: yes
-Macroscopic pathology: All animals were subjected to macroscopic examination which consisted of opening the cranial, abdominal and thoracic cavities. The macroscopic appearance of all tissues was recorded.
- Other examinations performed: histopathology


Statistics:
The acute median lethal oral dose (LD50) to male and female rats was calculated using the method of Finney (1971).

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1 539 mg/kg bw
95% CL:
1 206 - 1 965
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
1 373 mg/kg bw
95% CL:
1 174 - 1 607
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 453 mg/kg bw
95% CL:
1 221 - 1 729
Mortality:
All rats dosed at 2000 mg/kg and one female dosed at 1260 mg/kg died during the study. The majority of deaths occurred within the first six hours following dosing with a lesser number of rats expiring between approximately 24 and 48 hrs. after dosing.
Clinical signs:
Piloerection was observed in all rats within 6 min. of dosing. This sign persisted and was accompanied later on Day 1 and/or at later intervals during the study by:
-Hunched posture, waddling/unsteady gait, lethargy, pallid extremities, walking on toes, partially closed eyelids, respiratory distress, faecal disturbances, and ungroomed appearance observed among rats at all dosages,
-Dulled eyes, increased lacrimation and prostration noted in rats at 1260 and 2000 mg/kg only,
-Blue/cold extremities, body tremors, protruding eyes and swollen abdomen among rats at 2000 mg/kg only.

Recovery of surviving rats was complete by either Day 3 (females 800 mg/kg), Day 4 (males 800 mg/kg) or by Day 5 (1260 mg/kg).
Body weight:
All animals that survived treatment were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
Macroscopic examination of animals that died during the study revealed congestive changes (characterized by inflammation, darkened/pallid coloration, gaseous distension and liquid retention) in all or the majority of organs and tissues.
Macroscopic examination of animals surviving treatment and killed at study termination revealed no abnormalities.

Any other information on results incl. tables

The combined sexes slope of the probit line was 20.73 with standard error of 11.42 using log tranformation of dose. The heterogeneity factor was not significant.

The separate sexes slope of the parallel porbit lines was 22.91 with a standard error of 12.45 using log transformation of dose. The heterogeniety factor was not significant.

The chi-square test for parallelism gave no evidence of non-parallelism.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The rat oral LD50s( w/ 95% CI) were calculated to be :
Males: 1539 (1206 to 1965) mg/kg bodyweight
Females : 1373 (1174 to 1607) mg/kg bodyweight
Males and females : 1453 (1221 to 1729) mg/kg bodyweight