Tungsten

Acute Toxicity: oral

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

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tungsten

EC Number:

231-143-9

EC Name:

Tungsten

Cas Number:

7440-33-7

Molecular formula:

W

IUPAC Name:

tungsten

Constituent 2

Reference substance name:

Tungsten metal

IUPAC Name:

Tungsten metal

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 or test system 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:

other: 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 soi

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.