Reaction mass of 3-(3,3-dimethyl-2,3-dihydro-1H-inden-5-yl)propanal and 3-(1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)propanal and 3-(1,1-dimethyl-2,3-dihydro-1H-inden-4-yl)propanal

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Principles of method if other than guideline:

not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Taking effects as from 13th May 1998, until 29th January 2000

Test material

Test material information

Constituent 1

Reference substance name:

3-(3,3-dimethyl-2,3-dihydro-1H-inden-5-yl)propanal

Cas Number:

173445-65-3

Molecular formula:

C14H18O

IUPAC Name:

3-(3,3-dimethyl-2,3-dihydro-1H-inden-5-yl)propanal

Constituent 2

Reference substance name:

3-(1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)propanal

Cas Number:

173445-44-8

Molecular formula:

C14H18O

IUPAC Name:

3-(1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)propanal

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): ST 22 C 99
- Physical state: colourless liquid
- Storage condition of test material: at room temperature, protected from light and under nitrogen gas

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, 80160 Prouzel, France.
- Age at study initiation: not reported
- Weight at study initiation: on the day of treatment, the animals had a mean body weight ± standard deviation of 2.6 ±0.4 kg.
- Housing: individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm).
- Diet (e.g. ad libitum): free access to 112 C pelleted diet (UAR, 91360 Villemoissonsur-Orge, France).
- Water (e.g. ad libitum): drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum.
Bacteriological and chemical analyses of the water and diet, including the detection of possible contaminants (pesticides, heavy metals and nitrosamines), are performed regularly by external laboratories.
No contaminants were known to have been present in the diet or drinicing water at levels which may be expected to have interfered with or prejudiced the outcome of the study.
- Acclimation period: at least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3°C
- Humidity (%): 30 to 70%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air.
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: 1999-10-13 To: 1999-10-16

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
0.1 mL of the undiluted test substance was instilled into the conjuntival sac of the left eye of three rabbits.

Duration of treatment / exposure:

single exposure (the eyes were not rinsed after administration of the test item)

Observation period (in vivo):

The eyes were examined approximately 1 hour, 24, 48 and 72 hours after administration.

Number of animals or in vitro replicates:

3 male rabbits

Details on study design:

SCORING SYSTEM:
CONJUCTIVAE
Chemosis (A) : lids and/or nictitating membranes
0: - No swelling
1: - Any swelling above normal (includes nictitating membranes)
2: - Obvious swelling with partial eversion of lids
3: - Swelling with lids about half closed
4: - Swelling with lids more than half closed
Discharge (B) :
0: - No discharge
1: - slight discharge (does not include small amounts normally found in inner canthus)
2: - Discharge with moistening of the lids and hairs just adjacent
3: - Discharge with moistening of the lids and considerable area around the eye
Redness (C) : refers to palpebral and bulbar conjunctivae, cornea and iris
0: - Blood vessels normal
1: - Some blood vessels definitely hyperaemic (injected)
2: - Diffuse, crimson colour, individual vessels not easily discernible
3: - Diffuse beefy red
IRIS (D)
0: -Normal
1: - Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive)
2: - No reaction to light, haemorrhage, gross destruction (any or all of these)
CORNEA
Opacity (E) : degree of density (area most dense are taken for reading)
0: - No ulceration or opacity
1: - Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible
2: - Easily discernible translucent area, details of iris slightly obscured
3: - Nacreous area, no details of iris visible, size of pupil barely discernible
4: - Opaque cornea, iris not discernible through the opacity
Area of cornea involved (F)
1: - One-quarter (or less) but not zero
2: - Greater than one-quarter-less than one-half.
3: - Greater than one-half-less than three quarters
4: - Greater than three-quarters-up to whole area

Any other lesions observed were noted.

TOOL USED TO ASSESS SCORE: fluorescein (batch No. 9812), at 24h only.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Results 2

Irritation parameter:

conjunctivae score

Basis:

animal: #2 and #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 3

Irritation parameter:

chemosis score

Basis:

animal: #1 and #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 5

Irritation parameter:

iris score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 6

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Only very slight or slight (grade 1 or 2) conjunctival reactions (very slight or slight chemosis and very slight redness of the conjunctiva) were observed in all animals on day 1; they persisted for 24 hours in two animals. No other ocular reactions were observed during the study. See Table 7.3.2/1.

Other effects:

none

Any other information on results incl. tables

Table 7.3.2/1: Irritant/corrosive response data each animals at each observation time up to removal from the test

 

Score at time point / Reversibility	Cornea	Iris (/2)	Conjunctivae
	Opacity (/4)		Redness (/3)	Chemosis (/4)	Discharge (/3)
1 h	0 / 0 / 0	0 / 0 / 0	1 / 1 / 1	1 / 2 / 2	E
24 h	0 / 0 / 0	0 / 0 / 0	0 / 1 / 1	0 / 0 / 1	0 / 0 / 0
48 h	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0
72 h	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0
Average 24h, 48h, 72h	0 / 0 / 0	0 / 0 / 0	0.0 / 0.33 / 0.33	0.0 / 0.0 / 0.33	0 / 0 / 0
Reversibility*)	-	-	c.	c.	-
Average time for reversion	-	-	48 h	48 h	-

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 E = scoring masked by residual test substance

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test material induced very slight to slight irritation being reversible within 48 hours. Therefore the test material is not classified as irritant to the eyes according to the criteria of the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and of the GHS.

Executive summary:

In an eye irritation study performed according to the OECD guideline No. 404, and in compliance with GLP, 0.1 mL of test material was instilled into the left eye of 3 male New Zealand White rabbits. The eyes were not rinsed after the instillation of the test material. The right eye of each rabbit served as control. Animals were observed at 1 hour, 24, 48 and 72 hours after dosing. No further observation was performed since complete reversibility was achieved within 48 hours. The reactions in the conjunctiva (redness, chemosis and discharge), the iris and the cornea (opacity and area involved) were scored according to the Draize scale.

The individual score for each animal within 3 scoring times (24, 48 and 72 hours) were as follows: 0.0 / 0.33 / 0.33 for redness, 0.0 / 0.0 / 0.33 for chemosis.

No other ocular reactions were observed during the study.

Under the test conditions, the test material is not classified as irritating to eyes according to the criteria of the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and of the GHS.

This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.