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Administrative data

Description of key information

The acute toxicity of tantalum was investigated in guideline studies conducted according to OECD 423 respectively 403 addressing the oral and inhalation toxicity of the test material. Tantalum was tested orally at 2000 mg/kg bw and via the inhalation route at 5.18 mg/L without showing any adverse effects.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 September 2000 to 12 October 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
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 and environmental conditions:
TEST ANIMALS
- 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: Standard laboratory rodent diet ad libitum (Special Diet Services RM1(E) SQC expanded pellet)
- Water: ad libitum
- Acclimation period: 5 days (min.)
- Source: Harlan UK Ltd., Bicester, Oxon, England


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 ºC
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours artificial light (0600 - 1800 hours)

IN-LIFE DATES: From 26 September 2000 to 12 October 2000
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 females; 3 males
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.
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 2.
Body weight:
All animals were considered to have achieved satisfactory bodyweight gains throughout the study.
The data is summarised in Table 3.
Gross pathology:
No abnormalities were revealed at the macroscopic examination at study termination on day 15.

Table 2: 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 3: 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:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test accoridng to OECD 423, the acute median lethal oral dose to rats of the test material was demonstrated to be greater than 2000 mg/kg bw. The study is considered to be reliable, relevant and adequate for risk assessment and classification and labelling purposes.
Executive summary:

The acute oral toxicity of the test material was determined in accordance with the standardised guidelines OECD 423 and EU Method B.1. During the test, 3 male and 3 female rats received a single oral gavage dose of 2000 mg/kg bw test material, formulated at a concentration of 20 % w/v in 1 % w/v aqueous methylcellulose and administered at a volume of 10 mL/kg bw. During the study, animals were dosed and assessed for signs of toxicity for 14 days following dosing. Bodyweights were recorded at weekly intervals during the study. All animals were killed on day 15 for macroscopic examination post-mortem.

None of the animals died during the study and no significant clinical signs were observed. Furthermore, all animals gained weight during the study and no abnormalities were revealed at the macroscopic examination at study termination on day 15. The acute median lethal oral dose to rats of the test material was therefore demonstrated to be greater than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
GLP guideline study

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 October 2000 to 31 October 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
see "Principles of method if other than guideline"
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
yes
Remarks:
see "Principles of method if other than guideline"
Qualifier:
according to
Guideline:
other: J-MAFF test guidelines for acute inhalation studies
Deviations:
not specified
Principles of method if other than guideline:
The mass median aerodynamic diameter (MMAD) of the test aerosol was 4.6 µm. This volume 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 and environmental conditions:
TEST ANIMALS
- 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: SDS rat and mouse diet (RM1 (E) SQC expanded pellet) ad libitum.
- Water: Anglian tap water ad libitum.
- Acclimation period: 6 days
- Source: Charles River UK Limited, Manston Road, Margate, Kent, England.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 - 20.5 ºC
- Humidity (%): 39 - 65 %
- Air changes (per hr): 15 air changes/ hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light (06:00 - 18:00 GMT)
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 animals per sex per dose.
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: 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:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, the median lethal concentration of the test material was estimated to be in excess of 5.18 mg/L to male and female rats. The study is considered to be reliable, relevant and adequate for risk assessment and classification and labelling purposes.
Executive summary:

The acute inhalation toxicity of the test material was determined in accordance with the standardised guidelines OECD 403 and EPA OPPTS 870.1300. Five male and five female rats were exposed for a period of 4 hours to a particulate aerosol generated from the test material at a target concentration of 5 mg/L (5.18 mg/L measured). A further group, acting as a concurrent common control was exposed to clean air only.

During the 4 hour exposure period, and the 14 day post-exposure observation period, 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.

The median lethal concentration of the test material was estimated to be in excess of 5.18 mg/L to male and female rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5 180 mg/m³
Quality of whole database:
Three studies have been provided. Wilcox (2001) was selected as the key study as it was performed in compliance with GLP and standardised guidelines (Klimisch score 1).
Two further studies were provided as supporting information.
Firstly, a short abstract by Kammler (1972) reporting on the deposition of tantalum in the lungs. However, there is not sufficient information available to assess the reliability of the findings presented and hence a reliability score of 4 was assigned.
The study by Bianco (1974), in which dogs were administered with radiolabelled tantalum dust is also provided. The study was assigned a reliability score of 3 since data relate to a non-standard test method, reported in literature.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Oral:

The acute oral toxicity of the test material was determined in accordance with the standardised guidelines OECD 423 and EU Method B.1. During the test, 3 male and 3 female rats received a single oral gavage dose of 2000 mg/kg bw test material, formulated at a concentration of 20 % w/v in 1 % w/v aqueous methylcellulose and administered at a volume of 10 mL/kg bw. During the study animals were dosed and assessed for signs of toxicity for 14 days. Bodyweights were recorded at weekly intervals during the study. All animals were killed on day 15 for macroscopic examination post-mortem.

None of the animals died during the study and no significant clinical signs were observed. Furthermore, all animals gained weight during the study and no abnormalities were revealed at the macroscopic examination at study termination on day 15. The acute median lethal oral dose of the test material to rats was therefore estimated to be greater than 2000 mg/kg bw.

 

Inhalation:

During the key study, the acute inhalation toxicity of the test material was determined in accordance with the standardised guidelines OECD 403 and EPA OPPTS 870.1300. Five male and five female rats were exposed for a period of 4 hours, to a particulate aerosol generated from the test material at a target concentration of 5 mg/L (5.18 mg/L measured). A further group, acting as a concurrent common control was exposed to clean air only.

During the 4 hour exposure period, and the 14 day post-exposure observation period, no unscheduled deaths occurred. Clinical signs during the exposure period were limited to exaggerated breathing is 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. The median lethal concentration of the test material was estimated to be in excess of 5.18 mg/L to male and female rats.

Supporting information is available in the form of a short abstract by Kammler who reported that tantalum dust was observed to deposit in the lungs of dogs exposed to powdered tantalum (particle size 2 - 5 µm). However, retained tantalum was not found to cause unfavourable tissue reaction.

A further study by Bianco (1974) in which dogs were administered with radiolabelled tantalum dust, either by nose-only exposure or by intubation for a period of less than one hour, is included as supporting information. Findings indicate that tantalum had a prolonged retention time in the lungs with a mean biological removal half-time of greater than 2 years. Mucociliary transport, the dominant clearance mechanism was longer following tantalum exposure than exposure to other insoluble dusts. The study indicated a rapid early tracheobronchial phase and a later prolonged alveolar clearance phase. The study was assigned a reliability score of 3 since data relate to a non-standard test method, reported in the literature.


Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification for acute toxicity, as dosing at the limit dose for each of the two examined routes of exposure, oral and inhalation, failed to induce any toxic effects.