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Acute Toxicity: inhalation

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Administrative data

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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guidelineopen allclose all
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

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%
- Lot/batch No.: 20000804
- Storage condition of test material: in the dark at room temperature
- Expiry date: not advised but assumed to be stable for six months from date of receipt
- Sample received: 2000-08-25
- Purity test date: 2000-08-23

Test animals

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

Administration / exposure

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.

Results and discussion

Effect levels
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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.