Benzenamine, N,N-dimethyl-, oxidized, molybdatetungstatephosphates

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

old scoring system

Principles of method if other than guideline:

The study is disregarded due to the old and non-standard scoring system.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Benzenamine, N,N-dimethyl-, oxidized, molybdatetungstatephosphates

EC Number:

309-916-8

EC Name:

Benzenamine, N,N-dimethyl-, oxidized, molybdatetungstatephosphates

Cas Number:

101357-19-1

Molecular formula:

Reaction mass of C25 H30 N3. P Moy Wz O40 (y +z = 12) , C24 H28 N3. P Moy Wz O40 (y +z = 12) and C23 H26 N3. P Moy Wz O40 (y +z = 12)

IUPAC Name:

Reaction mass of [4-[bis[4-(dimethylamino)phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]-dimethyl-ammonium. molybdatetungstatephosphates, [4-[[4-(dimethylamino)phenyl]-[4-(methylamino)phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]-dimethyl-ammonium. molybdatetungstatephosphates and [4-[bis[4-(methylamino)phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]-dimethyl-ammonium. molybdatetungstatephosphates

Test material form:

solid: nanoform, no surface treatment

Details on test material:

SOURCE OF TEST MATERIAL
-Product number: 0345N (skin sensitisation, OECD 422, eye irritation, acute oral toxicity)
0345F (Ames test)

- Purity Preparation containing ≥80% (treat as 100%)
- Physical form/colour: Violet powder
- Expiry date: Stable for at least 5 years from delivery date

-Shape Category: spheroidal
-Shape: spherycal
-pure shape: yes
-Typical composition: ca. 100%
-range >50 and < 100%

-D10, typical value: 30 nm, range: >1.5 and < 50nm
-D50, typical value: 45 nm, range: >15 and <100nm
-D90, typical value: 60nm, range: >25 and < 150nm

-Fraction in size range 1-100nm: > 50 and <100%

-Crystallinity:
Structure:
amorphous, pure structure

-SSA: BET surface area typically ca. 32-40 m2/g for product number 345F and 0345N)
Range > 10 and < 200 m2/g

-.no surface treatment

Storage conditions: Stored at ambient conditions in the dark (away from direct light)
- Safety precautions: Routine hygienic procedures (nitrile gloves, goggles, face mask)

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: approximately twelve to sixteen weeks
- Weight at study initiation: 2.54 - 2.84 kg
- Housing: individually housed in suspended metal cages
- Diet: ad libitum, (RABMA Rabbit Diet, Special Diet Services Ltd., Witham, Essex, U.K.)
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 - 24°C
- Humidity: 56 - 75%
- Air changes: approximately 15 changes per hour
- Photoperiod: 12 hours light and 12 hours darkness

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL (approximately 88 mg)

Duration of treatment / exposure:

21 days

Observation period (in vivo):

21 days (oservations at 1 hour, 24, 48 and 72 hours; additional observations were made on days four, seven, fourteen and twenty-one to assess the reversibility of the ocular effects).

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM: Draize J.H. 1959, Association of Food and Drug Officials of the United States, Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics"

TOOL USED TO ASSESS SCORE: ophthalmoscope

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

not reversible

Remarks:

within 21 days

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 21 days

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

2.1

Max. score:

3

Reversibility:

not reversible

Remarks:

within 21 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Irritant / corrosive response data:

Areas of diffuse corneal opacity were noted in all treated eyes at the 24-hour observation with areas of diffuse to translucent corneal opacity at the 48 and 72-hour observations. Areas of translucent corneal opacity were noted in one treated eye at the 4-day observation. Opalescent corneal opacity over approximately 25% of the area with diffuse to translucent corneal opacity in the remaining area was noted in one treated eye at the 7-day observation. Areas of translucent corneal opacity were noted in one treated eye at the 7-day observation, in two treated eyes at the 14-day observation with diffuse to translucent corneal opacity at the 21-day observation. Vascularisation of the cornea was noted in two treated eyes at the 7, 14 and 21-day observations. The shape of the eyebal1 was distorted in two animals at the 14-day observation and persisted in one animal at the 21-day observation.
Iridial inflammation was noted in all treated eyes one hour after treatment and at the 24, 48 and 72-hour observations. Iridial inflammation was noted in one treated eye at the 4-day observation. Iridial inflammation was noted in two treated eyes at the 7 and 14-day observations.
Moderate conjunctival irritation was noted in all treated eyes one hour after treatment and at the 24 and 48-hour observations with moderate to severe conjunctival irritation at the 72-hour observation. Moderate conjunctival irritation was noted in one treated eye at the 4-day observation. Moderate conjunctival irritation was noted in two treated eyes at the 7 and 14-day observations with minimal to moderate conjunctival irritation at the 21-day observation. Sloughing of the conjunctival membranes was noted in one treated eye at the 4-day observation. Ectropion was noted in one treated eye at the 7-day observation and in two treated eyes at the 14 and 21-day observations.

Other effects:

- Other observations: Residual test material was noted around the treated eye of all animals throughout the study. Purple-coloured staining was noted in all treated eyes during the study. The staining did not affect evaluation of ocular effects.
Due to sloughing of the conjunctival membranes, one animal was killed for humane reasons immediately after the 4-day observation in accordance with current U.K. Home Office guidelines.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria