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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1998-03-24 to 1999-06-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Tungsten Metal Powder
- Physical state: Grey powder
- Analytical purity: >99%:

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan U.K. Ltd, Bicester, Oxon, England
- Age at study initiation: 4 to 7 wks
- Weight at study initiation: 94 to 112 g
- Fasting period before study: over-night prior to and 4 hrs after dosing
- Housing: in groups of 5 rats of the same sex in metal cages with wire mesh floors
- Diet: ad lib on Special Diet Services RM1(E) SQC expanded pellet
- Water:ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 to 22
- Humidity (%): 34 to 59
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1998-03-24 To: 1998-04-09

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 1% aqueous methylcellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20% w/v in 1% w/v aqueous methylcellulose
- MAXIMUM DOSE VOLUME APPLIED: 10mL/kg bodyweight

DOSAGE PREPARATION (if unusual):
Test substance was prepared on the day of dosing.

PRELIMINARY STUDY
2 rats (one female and one male) were treated at 1600 mg/kg bodyweight to establish a dosing regime for the main study.
Doses:
2000 mg/kg bodyweight.
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: 7 or 14 days
- Frequency of observations and weighing: Animals 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.
- The body weight of each rat was recorded on Days 1 (prior to dosing ), 8 and 15 or at death. Individual weekly bodyweight changes and group mean bodyweights were calculated.
- Necropsy of survivors performed: yes
- Clinical signs: The nature and severity of the clinical signs and time were recorded at each observation.
- Macroscopic pathology: All animals were subjected to a macroscopic examination, which consisted of opening the cranial, abdominal and thoracic cavities. The macroscopic appearance of all tissues was recorded.

Results and discussion

Preliminary study:
There were no deaths. Clinical signs included: piloerection and hunched posture was seen in both animals. There was increased sensitivity to touch observed in the male rat only. Bodyweight gains were considered satisfactory for studies of this nature and duration. No macroscopic abnormalities were noted at the terminal necropsy on Day 8 of this preliminary study. On the basis of the above findings, 2000mg/kg was selected as the dosage in the main study.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
In the main study, one female (out of a group of 10 rats-5 males and 5 females) died 2 days after a single oral administration of Tungsten Metal powder at a dose level of 2000 mg/kg. Macroscopic examination, where possible, revealed enlarged tissues and fluid contents in stomach.
Clinical signs:
Piloerection was observed in all rats within seven minutes of dosing. This sign persisted and was accompanied by hunched posture seen in all rats with abnormal faeces (characterised by soft to liquid faeces) and ungroomed appearance (characterised by soiled/stained fur around the ano/genital region) observed in one male only. There were no other signs of reaction to treatment and recovery was complete in all animals by Day 4.
Body weight:
Bodyweight gains were considered satisfactory for studies of this nature and duration.
Gross pathology:
No macroscopic abnormalities were noted at the terminal necropsy on Day 15.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral lethal oral dose (LD50) to rats of Tungsten Metal Powder was demonstrated to be greater than 2000 mg/kg bodyweight.