MoVNbTe mixed oxide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 December 2020 to 04 January 2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Since results of an ex vivo study on eye irritation indicated equivocal results and no stand-alone prediction can be made, a subsequent in vivo study was needed to fulfill the data requirements.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(Section 4: Health Effects), “Acute Eye Irritation/Corrosion” adopted on 09 October 2017 (Corrected on 26 June 2020)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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
- Batch No.of test material: 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)

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Adita Biosys Private Limited
- Age at study initiation: 4 months
- Weight at study initiation: 2.39066 kg to 2.42196 kg
- Housing: stainless steel wire mesh cage L 24 x B 18 x H 18 inches
- Diet (e.g. ad libitum): Altromin Maintenance diet for rabbits – Rich in crude fibre 2123
- Water (e.g. ad libitum): Deep bore-well water passed through reverse osmosis unit
- Acclimation period: Start: 21 December 2020 End: 31 December 2020

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.3°C to 22.8°C
- Humidity (%): 47% to 67%
- 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: 26 December 2020 To: 04 January 2021

Test system

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (weight with unit): Initial test: 45.2 mg and Confirmatory test: 47.6 mg and 49.1 mg

Duration of treatment / exposure:

1 hour

Observation period (in vivo):

1, 24, 48 and 72 hour

Number of animals or in vitro replicates:

3 (1 for initial test, 2 for confirmatory test)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: The eye was rinsed using 0.9% w/v normal saline after 1 hour treatment (post treatment)
- Time after start of exposure: 1 hour post test item instillation

SCORING SYSTEM: Cornea, area of cornea involved, iris, conjuctivae and chemoses was scored after 1, 24, 48 and 72 hour post test item instillation all with a maximum score of 4

TOOL USED TO ASSESS SCORE: hand-slit lamp and fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Other effects:

- Lesions and clinical observations: No clinical signs of toxicity and mortality were observed in both initial and confirmatory test animals

In both initial and confirmatory test, treated eye (left) revealed occular lesions like redness [Some blood vessels hyperaemic (injected)] at 1, 24 and 48 hour observation and chemosis (Some swelling above normal) at 24 hour observation. The observed lesion reversed back to normal by 72 hour observation

In both initial and confirmatory test, ocular lesion like conjunctivitis were observed at 24 and 48 hour observation. No ocular lesion was observed at 72 hour observation during slit lamp examination

- Effects of rinsing or washing: no effects on the eye due to washing

Any other information on results incl. tables

             TABLE 1. INDIVIDUAL ANIMAL CLINICAL SIGNS OF TOXICITY AND MORTALITY RECORD

Phase of the Experiment	Dose (mL/animal)	Animal No.	Sex	Clinical Signs of Toxicity and Mortality on Day
				1		2		3		4
				#	*	#	*	#	*	#
Initial Test	0.1	Nb5987	M	N	N	N	N	N	N	N
Confirmatory Test	0.1	Nb5988	M	N	N	N	N	N	N	N
	0.1	Nb5989	M	N	N	N	N	N	N	N

           M: Male; N: Normal; #: First observation; *: Second observation

            TABLE 2. INDIVIDUAL ANIMAL EYE IRRITATION/CORROSION SCORING RECORD

		Chemosis			Opacity			Area
Eyes		LE		RE		LE		RE		LE		RE		LE		RE		LE		RE
1 hr		1		0		0		0		0		0		0		0		-		-
24 hrs		1		0		1		0		0		0		0		0		-		-
48 hrs		1		0		0		0		0		0		0		0		-		-
72 hrs		0		0		0		0		0		0		0		0		-		-
Mean Tissue Score		0.67		0		0.33		0		0		0		0		0		-		-

hr: hour; hrs: hours; LE: Left Eye (Treated Eye); RE: Right Eye (Untreated/Reference control Eye);

Mean Tissue Score = (24 hr+48 hr+72 hr)/3

Redness: 0: Normal; 1: Some blood vessels hyperaemic (injected)

Chemosis:0: Normal; 1: Some swelling above normal

Iris:0: Normal               

Opacity:0: No ulceration or opacity

 

TABLE 2 (Contd...).  INDIVIDUAL ANIMAL EYE IRRITATION/CORROSION SCORING RECORD

Confirmatory Test                           Sex: Male                     Dose: 0.1 mL/animal      Animal No.:Nb5988
Observation Period	Ocular Lesions
	Conjunctiva				Iris		Cornea
	Redness		Chemosis				Opacity		Area
Eyes	LE	RE	LE	RE	LE	RE	LE	RE	LE	RE
1 hr	1	0	0	0	0	0	0	0	-	-
24 hrs	1	0	1	0	0	0	0	0	-	-
48 hrs	1	0	0	0	0	0	0	0	-	-
72 hrs	0	0	0	0	0	0	0	0	-	-
Mean Tissue Score	0.67	0	0.33	0	0	0	0	0	-	-

 

 

Confirmatory Test                           Sex: Male                     Dose: 0.1 mL/animal      Animal No.:Nb5989
Observation Period	Ocular Lesions
	Conjunctiva				Iris		Cornea
	Redness		Chemosis				Opacity		Area
Eyes	LE	RE	LE	RE	LE	RE	LE	RE	LE	RE
1 hr	1	0	0	0	0	0	0	0	-	-
24 hrs	1	0	1	0	0	0	0	0	-	-
48 hrs	1	0	0	0	0	0	0	0	-	-
72 hrs	0	0	0	0	0	0	0	0	-	-
Mean Tissue Score	0.67	0	0.33	0	0	0	0	0	-	-

hr: hour; hrs: hours; LE: Left Eye (Treated Eye); RE: Right Eye (Untreated/Reference control Eye)

Mean Tissue Score = (24 hr+48 hr+72 hr)/3

Redness: 0: Normal; 1: Some blood vessels hyperaemic (injected)

Chemosis:0: Normal; 1: Some swelling above normal

Iris:0: Normal               

Opacity:0: No ulceration or opacity

                                       TABLE 3.  INDIVIDUAL ANIMAL SLIT LAMP EXAMINATION RECORD

Initial Test                   Sex: Male                       Dose: 0.1 mL/animal                         Animal No.: Nb5987
	Day 2 (24 hours)		Day 3 (48 hours)		Day 4 (72 hours)
Eye	LE	RE	LE	RE	LE	RE
Lids	13	N	13	N	N	N
Ducts	N	N	N	N	N	N
Cornea	N	N	N	N	N	N
Pupil	N	N	N	N	N	N
Sclera	N	N	N	N	N	N
Ciliary Bodies	N	N	N	N	N	N
Iris	N	N	N	N	N	N
Aqueous Humour	N	N	N	N	N	N
Lens	N	N	N	N	N	N
Vitreous Humour	N	N	N	N	N	N

LE: Left Eye; RE: Right Eye; N: Normal/No Abnormality Detected; 13: Conjunctivitis

 

  

TABLE 3 (Contd…). INDIVIDUAL ANIMAL SLIT LAMP EXAMINATION RECORD

Confirmatory Test                   Sex: Male                       Dose: 0.1 mL/animal            Animal No.: Nb5988
	Day 2 (24 hours)		Day 3 (48 hours)		Day 4 (72 hours)
Eye	LE	RE	LE	RE	LE	RE
Lids	13	N	13	N	N	N
Ducts	N	N	N	N	N	N
Cornea	N	N	N	N	N	N
Pupil	N	N	N	N	N	N
Sclera	N	N	N	N	N	N
Ciliary Bodies	N	N	N	N	N	N
Iris	N	N	N	N	N	N
Aqueous Humour	N	N	N	N	N	N
Lens	N	N	N	N	N	N
Vitreous Humour	N	N	N	N	N	N

 

 

Confirmatory Test                   Sex: Male                       Dose: 0.1 mL/animal            Animal No.: Nb5989
	Day 2 (24 hours)		Day 3 (48 hours)		Day 4 (72 hours)
Eye	LE	RE	LE	RE	LE	RE
Lids	13	N	13	N	N	N
Ducts	N	N	N	N	N	N
Cornea	N	N	N	N	N	N
Pupil	N	N	N	N	N	N
Sclera	N	N	N	N	N	N
Ciliary Bodies	N	N	N	N	N	N
Iris	N	N	N	N	N	N
Aqueous Humour	N	N	N	N	N	N
Lens	N	N	N	N	N	N
Vitreous Humour	N	N	N	N	N	N

LE: Left Eye; RE: Right Eye; N: Normal/No Abnormality Detected; 13: Conjunctivitis

 

   TABLE 4.   INDIVIDUAL ANIMAL BODY WEIGHT (kg) AND PERCENT CHANGE IN BODY WEIGHT WITH RESPECT TO DAY 1

Phase of the Experiment	Dose (mL/animal)	Animal No.	Sex	Body Weight (kg) on Day		Percent Change in Body Weight with Respect to Day
				1	4	1 to 4
Initial Test	0.1	Nb5987	Male	2.47619	2.51406	1.52937
Confirmatory Test	0.1	Nb5988	Male	2.49617	2.52473	1.14415
	0.1	Nb5989	Male	2.51403	2.54009	1.03658
			Mean	2.50510	2.53241	1.09037
			±SD	0.01263	0.01086	0.07606
			n	2	2	2

 SD: Standard deviation; n: Number of animals

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the above results of the experiment and under the experimental conditions employed, it is concluded that the mean score of the test item does not meet classification criteria and hence not classified or categorized as per the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Executive summary:

The test item was evaluated for Acute Eye Irritation/Corrosion in New Zealand White Rabbits.

The study was performed in two phases i.e., initial and confirmatory tests. Both the eyes of each experimental animal was examined within 24 hours before the treatment. The animals with absence of signs of eye irritation, ocular defects or pre-existing corneal injury were used for the treatment. The pH of test item was 3.08 as per in-house pH determination.

 

The initial test was conducted using single male rabbit and confirmatory test was conducted using two male rabbits. The systemic analgesic (tramadol hydrochloride injection 2.5 mg/kg) and two drops of topical ocular anaesthetic (0.5% tetracaine hydrochloride) were given to each animal sixty minutes and five minutes prior to test item instillation respectively. The 0.1 mL (Initial test: 45.2 mg and Confirmatory test: 47.6 mg and 49.1 mg) of test item was instilled into the conjunctival sac of the left eye and right eye served as control. The eyes were scored approximately at 1, 24, 48 and 72 hours. Slit lamp examination was carried out using fluorescein strips (fluorescein sodium ophthalmic strip USP) and were scored approximately at 24, 48 and 72 hours for both initial and confirmatory test.

 

All the animals (initial test and confirmatory test) were observed twice daily for clinical signs of toxicity and mortality. No treatment related clinical signs of toxicity and mortality were observed in all the animals (initial and confirmatory tests) after the test item instillation.

 

In both initial and confirmatory test, treated eye (left) revealed occular lesions like redness at 1, 24 and 48 hour; chemosis at 24 hour observation. The observed lesion reversed back to normal by 72 hour observation.

 

In both initial and confirmatory test, ocular lesion like conjunctivitis were observed at 24 and 48 hour observation. No ocular lesion was observed at 72 hour observation during slit lamp examination.

 

The body weight was recorded on the day of receipt, on the day of treatment (prior to instillation of test item) and at termination of the experiment. No changes were noted in body weight and percent change in body weight with respect to day 1 in both initial and confirmatory test. All the animals revealed physiologically normal increase in body weight in both initial and confirmatory tests.

 

All the animals were sacrificed by intravenous administration of sodium thiopentone and carcass was disposed.

 

For initial test and confirmatory test, the mean score calculated across 3 scoring times (approximately 24, 48 and 72 hours after test item instillation) for cornea, iris and conjunctival redness and conjunctival chemosis were 0, 0, 0.67 and 0.33 respectively