Tantalum carbide

Endpoint summary

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:

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.

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.