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Description of key information

In an acute oral toxicity according to OECD 423 no mortality was observed in rats at concentrations of 2000 mg tantalum/kg bw. 
In an acute inhalation toxicity study according to OECD 403 conducted with tantalum and tantalum pentoxide no mortality occurred in rats at the highest practicable concentrations (5.18 mg/L and 3.89 mg/L tantalum and tantalum pentoxide, respectively).
Tantalum and tantalum pentoxide data are used in read-across approach in the assessment of the acute toxicity of tantalum carbide.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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.
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
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
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.
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:
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 (females) or day 3 (males).
Clinical signs are summarised in Table 1.
Body weight:
All animals were considered to have achieved satisfactory bodyweight gains throughout the study.
The data is summarised in Table 2.
Gross pathology:
No abnormalities were revealed at the macroscopic examination at study termination on day 15.
Other findings:
N.A.

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

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Ta data are used in a read-cross approach in the assessment of TaC.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2000-09-25 to 2001-03-20
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study. Tantalum used as read-across partner to Tantalum carbide.
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
; see text box below
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
yes
Remarks:
; see text box below
Principles of method if other than guideline:
The mass median aerodynamic diameter (MMAD) of the test aerosol was 4.6 µm. This MMAD is slightly in excess of the guideline maximum of 4.0 µm. However it is considered that the value obtained was the minimum practical at the concentration achieved given the nature of the test material.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Limited, Margate, England
- Age at study initiation: 7 and 8 weeks (males and females respectively)
- Housing: by sex, in groups of 5 in holding cages made of stainless steel sheet and wire mesh suspended on a movable rack
- Diet: ad libitum
- Water: tap water ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 - 20.5
- Humidity (%): 39 - 65
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: a Wright Dust Feed mechanism was used to produce and maintain atmospheres containing a particulate aerosol by suspending material scraped from the surface of a compressed powder in a stream of dry air. The concentration of particulate aerosol was altered by changing the rate at which the scraper blade is advanced into the compressed powder held in the test material canister. The Wright Dust Feed was mounted on a glass cylinder attached to the top of the exposure chamber. The conditioned test atmosphere entered through a port at the top centre of the chamber and passed out through a port at the base section below the level of the rats.
- Exposure chamber volume: 30 L
- Method of holding animals in test chamber: snout-only exposure chambers (animals held in moulded polycarbonate restraining tubes and held in a forward position by an adjustable foamed plastic stopper, which also provided a seal for the tube)
- Source and rate of air: clean, dry air was passed through an electronic neutraliser, connected to a generator and the supply pressure adjusted to give a flow rate of 16 litre/minute. An in-line flow meter was used to monitor the generator air supply throughout the exposure. The exhaust airflow was calibrated and adjusted to produce a slightly negative pressure.
- Method of particle size determination: particle size measured with a Marple cascade impactor. The volume of air sampled was measured using a wet-type gas meter. The amount of material collected on the stages of the sampler was determined gravimetrically. The particle size distribution of the test atmosphere was then assessed using linear regression analysis.
- Treatment of exhausted air: the exposure system was positioned inside a large cabinet equipped with an extract fan exhausting to atmosphere through an absolute filter.
- Temperature and humidity in air chamber: 20.0 - 20.1 °C, 42 - 58 % (mean values)

TEST ATMOSPHERE
- Brief description of analytical method used: five samples of air were removed from the test chamber following equilibration and hourly thereafter. Each air sample was withdrawn at a rate of 2 L/min through a pre-weighed glass fibre filter. The volume of air sampled was measured using a wet-type gas meter. The filters were reweighed following sampling for gravimetric analysis of the test aerosol.

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter): 4.6 µm (approximately 67 % of the aerosol generated consisted of particulate of size < 7 µm)

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
The nominal concentration was 92.2 mg/L. The mean chamber concentration was 5.6 % of the nominal concentration that reflects losses of the test material due to impaction, deposition and cohesion due to static within the exposure system. The mean chamber concentration of total particulate was 5.18 mg/L and was in good agreement with target (5 mg/L).
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days.
- Environmental conditions in the exposure chamber: air temperature was measured using an alcohol-in-glass thermometer and relative humidity was measured using a Casella type T6900 relative humidity meter. The temperature and relative humidity were recorded at the start of exposure and then at 30 minute intervals during the 4 hour exposure.
- Frequency of observations and weighing: throughout the study, all cages were checked at least twice daily for dead or moribund animals. Rats were observed intermittently for signs of reaction to the test material during exposure and at least twice daily throughout the observation period. Clinical signs were recorded at the end of the chamber equilibration period, at 0.25, 0.5 and 1.0 hours then hourly during the exposure. Clinical signs were recorded immediately following exposure and then at 1.0 and 2.0 hours post-exposure. During the observation period, clinical signs were recorded twice daily. Bodyweights were recorded twice during the week prior to exposure (day 0) and then weekly during the observation period and on the day of death.
- Necropsy of survivors performed: yes.
- Other examinations performed: at the end of the 14-day observation period, the rats were killed by intraperitoneal injection of pentobarbitone sodium followed by exsanguinations from the brachial blood vessels and subjected to a detailed macroscopic examination. The lungs (including the larynx and trachea) were removed, dissected clear of surrounding tissue, weighed and the weights recorded.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.18 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
There were no unscheduled deaths.
Clinical signs:
other: DURING EXPOSURE: - Exaggerated breathing was observed in a proportion of test rats from 15 minutes and in all test rats from 30 minutes into exposure. Grey staining of the fur was noted for all test rats from 3 hours into exposure. Soiling of the fur wit
Body weight:
There were no treatment-related effects.
Gross pathology:
There were no treatment-related effects at necropsy.
Incidental effects noted included: small dark foci noted on the lungs of two male test rats and a male control rat. Hair loss from head was noted for a male test rat.
Other findings:
Lung weight: there were no treatment-related effects.

Table 1: Chamber Concentration of Test Material

Sample Time taken (h:min) Gravimetric conc. (mg/L) Nominal conc. (mg/L)
1 0:10 4.95
2 1:00 5.00
3 2:00 5.48
4 2:58 5.04
5 3:54 5.41
Mean 5.18 92.2
SD 0.249

Table 2: Particle Size Distribution of Test Material

Sample Time taken (h:min) Stage Cut-off size (µm) Amount collected (mg)
PSD 1 1:31 1 21.30 0.06
2 14.80 0.07
3 9.80 0.35
4 6.00 0.63
5 3.50 0.34
6 1.55 0.26
7 0.93 0.01
8 0.52 0.00
Filter 0.00 0.08
Total 1.80
PSD 2 3:31 1 21.30 0.00
2 14.80 0.09
3 9.80 0.39
4 6.00 0.77
5 3.50 0.40
6 1.55 0.29
7 0.93 0.06
8 0.52 0.03
Filter 0.00 0.08
Total 2.11

Table 3: Calculations
Cut-off size (µm) % less than size (cumulative)
PSD 1 PSD 2 Combined
 
21.30 96.60 100.00 98.50
14.80 92.70 95.70 94.40
9.80 73.30 77.20 75.50
6.00 38.30 40.70 39.70
3.50 19.40 21.70 20.80
1.55 5.00 8.00 6.70
0.93 4.40 5.20 4.90
0.52 4.40 3.80 4.10
MMAD (µm) 5.10 4.00 4.60
geometric SD 2.66 2.28 2.53
% respirable (< 7 µm) 62.00 75.00 67.00

SD= standard deviation

Table 4: Individual and Group Mean Bodyweights

Group Rat Day of observation
-7 -4 -2 -1 0 7 14
1 M (Control) 101 215 246 268 278 331 377
102 221 253 277 284 331 368
103 223 245 274 280 332 349
104 235 265 288 298 350 386
105 228 265 292 295 359 404
Mean 224 255 280 287 341 377
2 M (Test) 81 219 239 258 306 352
82 220 239 257 297 332
83 228 243 261 299 335
84 228 249 263 300 343
85 218 235 253 300 343
Mean 223 241 258 300 341
1 F (Control) 106 204 223 234 237 256 265
107 189 199 199 204 209 205
108 208 220 228 229 243 252
109 204 222 225 233 255 255
110 209 222 231 236 245 247
Mean 203 217 223 228 242 245
2 F (Test) 86 199 215 222 238 242
87 205 211 212 227 235
88 203 207 216 233 237
89 208 212 219 222 211
90 196 205 209 218 229
Mean 202 210 216 228 231
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In conclusions, in acute inhalation study in rats the LC50 after nose-only exposure to Tantalum was estimated to be greater than 5.18 mg/L.
Executive summary:

In an acute inhalation toxicity study (OECD 403), groups of young adult Sprague Dawley rats (5/sex) were exposed nose-only to Tantalum (99.9%) for 4 hours at a concentration of 5.18 mg/L. Animals then were observed for 14 days. A further group, acting as a concurrent common control was exposed to clean air only. No unscheduled deaths occurred. Clinical signs during the exposure period were limited to exaggerated breathing in test rats 15 to 30 minutes into exposure and grey staining on the fur 3 hours into exposure. During the observation period, clinical signs were limited to exaggerated breathing in all test rats immediately post exposure, persisting to day 4 of the observation period. A black/grey substance on the fur of the snout and jaws was evident on all test animals, persisting to day 2 of the observation period and hair loss from head of a single male test rat on day 14 of the observation period. All animals gained weight during the study. There were no macroscopic abnormalities at examination post mortem. Based on the results, LC50 was estimated to be greater than 5.18 mg/L for both male and female rats.

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

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
No deaths occured after 4h exposure of rats by Ta and Ta2O5, respectively. Test substance concentrations were higher in the study conducted with Ta (exposure concentration of test item itself as well as converted to concentration of TaC). Thus this study is considered to be the key study for the risk assessment of TaC (read-across approach).

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Tantalum and tantalum pentoxide were used to assess in a read across approach the acute toxicity of tantalum carbide. Assuming that tantalum is the crucial component of tantalum carbide for the toxicity assessment, both tantalum and tantalum pentoxide serve the purpose of toxicity assessment as they are of higher solubility in water than tantalum carbide. Therefore the applied doses of tantalum by treatment with either tantalum of tantalum pentoxide fulfil the requirements of test dosages specified in OECD guidelines 404 and 405.

In an acute oral toxicity according to OECD 423 rats showed no mortality after treatment with tantalum at a dose of 2000 mg/kg bw. Thus the oral LD50 can be considered to be greater than 2000 mg/kg bw. In an acute inhalation toxicity study according to OECD 403 rats were exposed nose only to the source substances tantalum and tantalum pentoxide for 4 hours and were afterwards observed for 14 days. No mortality occurred at the highest concentration which was possible to generate. Thus, the LC 50 for tantalum is considered to be greater than 5.18 mg/L and the LC 50 after inhalation of tantalum pentoxide is considered to be greater than 3.89 mg/L.

For a detailed description of the read-across approach please refer to the read-across report.


Justification for selection of acute toxicity – oral endpoint
GLP guideline study according to OECD 423

Justification for selection of acute toxicity – inhalation endpoint
GLP guideline study according to OECD 403

Justification for classification or non-classification

The target substance tantalum carbide does not warrant classification for acute toxicity as no mortality occurred after treatment with the suitable read-across partner in acute toxicity studies according to OECD 423 and OECD 403.