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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2000-09-23 to 2000-12-18
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study. Tantalum used as read-across partner to Tantalum carbide.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Tantalum
EC Number:
231-135-5
EC Name:
Tantalum
Cas Number:
7440-25-7
IUPAC Name:
tantalum(2+)
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Ta MP STA-40 KD
- Physical state: grey powder
- Analytical purity: 99.9%
- Storage condition of test material: room temperature
- Expiry date: not advised but assumed to be stable for six months from date of receipt
- Sample received: 2000-08-25

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: 5 - 7 weeks
- Weight at study initiation: 92 - 115 g
- Fasting period before study: overnight prior to and approximately 4 hours following dosing
- Housing: in groups of three by sex in metal cages with mesh floors
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days (min.)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 1 % w/v aqueous methylcellulose
Details on oral exposure:
VEHICLE - 1 % w/v aqueous methylcellulose

DOSE VOLUME APPLIED: 10 mL/kg bw

TEST MATERIAL PREPARATION: the test material was formulated at a concentration of 20 % w/v in 1 % w/v aqueous methylcellulose and administered at a volume of 10 mL/kg bw. The test material was prepared on the day of dosing.

The appropriate dose volume of the test material was administered to each rat by oral gavage using a plastic syringe and catheter (8 ch). The day of dosing was designated day 1.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Treatment procedure: a group of three fasted female rats received the limit dose. As results at this dosage indicated the acute lethal oral dose to be greater than 2000 mg/kg bodyweight, in compliance with the study guidelines, a group of three fasted males was dosed at 2000 mg/kg to confirm the results and complete the study.

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Mortality was checked at least twice daily while animals were observed for clinical signs soon after dosing and at frequent intervals for the remainder of day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day. The nature and severity of the clinical signs and time were recorded at each observation. The bodyweight of each rat was recorded on days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.

- Necropsy of survivors performed: yes - all animals were killed on day 15 by carbon dioxide asphyxiation and subjected to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of all examined organs was recorded.
Statistics:
N.A.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths during the study.
Clinical signs:
other: Clinical signs of reaction to treatment were confined to piloerection and hunched posture, seen in all rats, with abnormal gait observed in all females. Recovery of rats, as judged by external appearance and behaviour, was complete by either day 2 (female
Gross pathology:
No abnormalities were revealed at the macroscopic examination at study termination on day 15.
Other findings:
N.A.

Any other information on results incl. tables

Table 1: Signs of Reaction to Treatment

Clinical signs No of rats in groups of 3 showing signs
Male Female
Piloerection 3 3
Hunched posture 3 3
Abnormal gait 0 3

Table 2: Individual Bodyweights and Bodyweight Gains

Dose (mg/kg) Sex Animal No. Bodyweight (g) on day Bodyweight gains (g) on day
1* 8 15 8 15
2000 Male 4 109 185 237 76 52
5 100 164 213 64 49
6 115 184 237 69 53
Mean 108 178 229
Female 1 98 142 166 44 24
2 92 134 157 42 23
3 98 137 160 39 23
Mean 96 138 161

*Prior to dosing

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In conclusion, in an acute oral toxicity study (OECD 423), the LD50 value in rats after oral Tantalum treatment was greater than 2000 mg/kg body weight.
Executive summary:

In an acute oral toxicity study (OECD 423), groups of fasted Sprague Dawley rats (3/sex) were given a single dose of Tantalum (99.9 %) in 1% w/v aqueous methylcellulose at a dose of 2000 mg/kg bw and were observed for 14 days. There were only mild signs of toxicity oberserved and a full recovery of rats was completed by either day 2 (females) or day 3 (males). No mortality occurred. Based on the results from this study, the LD50 in rats after Tantalum treatment is considered to be greater than 2000 mg/kg bw.

This information is used in a read-across approach for the assessment of tantalum carbide.