MoVNbTe mixed oxide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 October 2020 to 18 November 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

OECD Guidelines for Testing of Chemicals No. 403 – Traditional Protocol “Acute Inhalation Toxicity” adopted on 07 September 2009

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

traditional method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

niobium trivanadium decamolybdenum tellurium dotetracontaoxide

EC Number:

888-364-4

Cas Number:

146569-48-4

Molecular formula:

Mo10V3Nb1Te1O42

IUPAC Name:

niobium trivanadium decamolybdenum tellurium dotetracontaoxide

Test material form:

solid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and batch No.of test material: Clariant Produkte (Deutschland) GmbH
83052 Bruckmühl/Heufeld
Germany
and EX.14402.600
- Expiration date of the batch: No change of properties known over time (endless)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Ambient (21 to 29°C)

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Aerosol
- Preliminary purification step (if any): No

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: In-house
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 10 weeks
- Weight at study initiation: Males : 183.27 g to 191.12 g
Females : 167.28 g to 175.15 g
- Fasting period before study: No
- Housing: standard polypropylene cage (size: L 430 × B 285 × H 150 mm)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 29 October 2020 to 03 November 2020

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.0°C to 22.9°C
- Humidity (%): 49% to 64%
- Air changes (per hr): 12 to 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light and 12 hours dark cycle

IN-LIFE DATES: From: 29 October 2020 To: 18 November 2020

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

clean air

Mass median aerodynamic diameter (MMAD):

> 2.86 - <= 3.18 µm

Geometric standard deviation (GSD):

> 2.55 - <= 2.58

Remark on MMAD/GSD:

All the values were within the acceptable range

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: flow-past, nose-only dynamic inhalation exposure system supplied by CH Technologies, USA
- Exposure chamber volume: 0.76 L
- Method of holding animals in test chamber: restrainer
- Source and rate of air: compressor air and 20 L/min
- Method of conditioning air: purified air
- System of generating particulates/aerosols: Palas RBG 1000
- Method of particle size determination: 7 stage cascade mercer impactor
- Treatment of exhaust air: NaOH
- Temperature, humidity, pressure in air chamber: 22.4 to 22.6°C, 55.3 to 55.9%, 60psi

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetrically
- Samples taken from breathing zone: yes

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: Based on technical pre-test and achieved limit concentration i.e., 5 mg/L.

Analytical verification of test atmosphere concentrations:

no

Remarks on duration:

4 hours exposure

Concentrations:

Limit concentration 5 mg/L

No. of animals per sex per dose:

3 males and 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: once daily thereafter for clinical signs and twice daily for mortality and weighing on day 1, 2, 4, 8 and 15
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.04 mg/L air

Based on:

test mat.

Body weight:

No substance related changes were observed in body weight and percent change in body weight with respect to day 1 at the mean maximum achievable concentration of 5.04 mg/L of air. However, all animals showed slight decrease in body weight on day 2 due to restraining of animals during exposure. This slight change was transient and no clinical signs were observed during the experimental period. All animals increased in body weight from day 4 onwards

Gross pathology:

No treatment related gross pathological findings were observed at the maximum achievable concentration of 5.04 mg/L of air

Any other information on results incl. tables

 

TABLE 1.     CLINICAL SIGNS AND MORTALITY RECORD

Group  & Concentration (mg/L of air)

Animal No.

Sex

Day 1

Days

During Exposure

Post exposure

1 hr*

2 hrs*

3 hrs*

4 hrs*

30-40 min

1 hr*

2

3

4

5

6

7

8

9

10

11

12

13

14

15

Limit Test & 5.04

Re9026

M

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Re9027

M

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Re9028

M

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Re9029

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Re9030

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Re9031

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

           *: ± 10 minutes; N: Normal; M: Male; F: Female; min: minute; hr(s): hour(s)

 

                       

 

TABLE 2.     BODY WEIGHT (g) AND PERCENT CHANGE IN BODY WEIGHT (%) WITH RESPECT TO DAY 1

Group &   Concentration (mg/L of air)		Animal No.		Sex		Body Weight (g) on Days								Percent Change in Body Weight with Respect to Day 1
			1^#			2		4		8		15				1-2		1-4		1-8		1-15
Limit Test & 5.04		Re9026		M		202.42		200.20		203.27		216.43		238.59				-1.10		0.42		6.92		17.87
		Re9027		M		211.59		209.87		213.11		227.74		249.45				-0.81		0.72		7.63		17.89
		Re9028		M		206.11		205.46		207.65		221.55		247.01				-0.32		0.75		7.49		19.84
		Mean				206.71		205.18		208.01		221.91		245.02				-0.74		0.63		7.35		18.54
		(±) SD				4.61		4.84		4.93		5.66		5.70				0.40		0.18		0.38		1.13
		n				3		3		3		3		3				3		3		3		3
		Re9029		F		182.63		180.22		184.83		193.16		210.09				-1.32		1.20		5.77		15.04
		Re9030		F		191.80		189.30		193.42		203.88		214.76				-1.30		0.84		6.30		11.97
		Re9031		F		186.47		185.06		188.09		199.60		212.69				-0.76		0.87		7.04		14.06
		Mean				186.97		184.86		188.78		198.88		212.51				-1.13		0.97		6.37		13.69
		(±) SD				4.61		4.54		4.34		5.40		2.34				0.32		0.20		0.64		1.57
		n				3		3		3		3		3				3		3		3		3

#: Prior to exposure;M: Male; F: Female;SD: Standard Deviation, n: Number of animals

TABLE 3.     BREATHING ZONE CONCENTRATION (ACTUAL TEST ITEM CONCENTRATION)

Technical Pre-test:

Sl. No.		Feed rate (mm/hour)		Rotation (rpm)		Initial weight (mg) (a)		Final weight (mg) (b)		Difference (mg) (c) = (b) – (a)		Air Flow Rate (L/min) (d)		Time (min) (e)		BZC (mg/L of air)		Mean BZC (mg/L of Air)
1		012		600		345.61		349.85		4.24		0.84		1		5.05		5.05
2		012		600		346.60		350.85		4.25		0.84		1		5.06

Limit Test:

Sl. No.		Feed rate (mm/hour)		Rotation (rpm)		Initial weight (mg) (a)		Final weight (mg) (b)		Difference (mg) (c) = (b) – (a)		Air Flow Rate (L/min) (d)		Time (min) (e)		BZC (mg/L of air)		Mean BZC (mg/L of Air)
1		012		600		346.63		350.85		4.22		0.84		1		5.02		5.04
2		012		600		343.84		348.09		4.25		0.84		1		5.06
3		012		600		349.44		353.67		4.23		0.84		1		5.04

 BZC: Breathing Zone Concentration; Sampled volume: 0.84 L/min; Sampling time: 1 minute

 

BZC (f) =		Mass of test item collected on the filter paper (c)
		Volume of air passed through the filter paper (d) X time (e)

 

 

 

 

TABLE 4.     CHAMBER (EXPOSURE) CONDITIONS

Technical Pre-test:

Concentration (mg/L of air)	SL. No.	Feed rate (mm/hour)	Rotation (rpm)	Temperature (°C)	Relative Humidity (%)	Oxygen Concentration (%)	Carbon dioxide Concentration (ppm)	Air Flow (L/min)
5.05	1	012	600	22.7	55.6	20.2	615	20
	2	012	600	22.4	56.2	20.5	612	20

 

Limit Test:

Concentration (mg/L of air)	SL. No.	Feed rate (mm/hour)	Rotation (rpm)	Temperature (°C)	Relative Humidity (%)	Oxygen Concentration (%)	Carbon dioxide Concentration (ppm)	Air Flow (L/min)
5.04	1	012	600	22.6	55.9	20.4	618	20
	2	012	600	22.4	55.7	20.3	619	20
	3	012	600	22.5	55.3	20.2	620	20

Note: 1% Carbon dioxide = 10000 ppm

 

 

TABLE 5.     GROSS PATHOLOGICAL FINDINGS

Group &Concentration (mg/L of air)	Animal No.	Sex	Fate	Gross Pathology Findings
				External	Internal
Limit Test & 5.04	Re9026	M	TS	NAD	NAD
	Re9027	M	TS	NAD	NAD
	Re9028	M	TS	NAD	NAD
	Re9029	F	TS	NAD	NAD
	Re9030	F	TS	NAD	NAD
	Re9031	F	TS	NAD	NAD

NAD: No Abnormality Detected; M: Male; F: Female; TS: Terminal Sacrifice

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions employed and based on the above results of experiment, there were no clinical signs and mortality observed at mean maximum achievable concentration of 5.04 mg/L of air. Hence, the LC50 of the test item is > 5.04 mg/L of air. This result, taking into account that there is no identification of a harm of acute nature towards vulnerable populations, does not justify a classification according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Executive summary:

The test item was evaluated for acute inhalation toxicity in Sprague Dawley rats.

The objective of the study was to assess the toxic potential and to determine the LC50 of test item when administered by inhalation route through flow-past nose-only dynamic inhalation equipment for a single 4 hours exposure to rats. Three male and three female rats were used for conducting the acute inhalation toxicity study.

As such test item was used during technical pre-test and limit test to generate the dust aerosols through rotating brush generator. The technical pre-test was carried out without animals. During the technical pre-test, the target concentration i.e. 5.04 mg/L of air was achieved.

During the exposure period, the temperature, relative humidity, oxygen and carbon dioxide concentration of the chamber were 22.4°C to 22.6°C, 55.3% to 55.9%, 20.2% to 20.4% and 618 ppm to 620 ppm (0.06%) respectively for limit test. The particle size MMAD and GSD were 2.86 µm to 3.18 µm and 2.55 to 2.58 respectively. All the values were within theacceptablerange. The mean maximum achievable breathing zone concentration (actual concentration) was 5.04 mg/Lof airand it was considered as the limit concentration.

All the animals were observed for clinical signs and pre-terminal deaths at 1 hr (±10 mins), 2 hrs (±10 mins), 3 hrs (±10 mins) and 4 hrs (±10 mins) during exposure and 30 to 40 minutes and 1 hour (±10 mins) post-exposure on day 1 and once daily thereafter for clinical signs and twice daily for mortality till 14 days post exposure period.Individual animal body weight was recorded on day 1 (on the day of exposure) prior to the exposure and on day 2, 4, 8 and 15. During exposure period, the chamber (exposure) conditions were recorded. All rats were euthanized after 14 days post exposure period by intraperitoneal administration of sodium thiopentone and the gross pathological findings were recorded.

No treatment related clinical signs of toxicity and mortalities were observed. Slight decrease in body weight was noted on Day 2 due to exposure. All animals showed increase in body weight on day 4, 8 and 15.

No treatment related gross pathological findings were observed atthe mean maximum achievable concentration of 5.04mg/L of air.

 

This result, taking into account that there is no identification of a harm of acute nature towards vulnerable populations, does not justify a classification according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).