Propan-2-ol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented, according to accepted guidelines

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

study terminated at 14 days instead of 21 with complete revisibility only seen in 3 of 6 animals

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Propan-2-ol

EC Number:

200-661-7

EC Name:

Propan-2-ol

Cas Number:

67-63-0

Molecular formula:

C3H8O

IUPAC Name:

propan-2-ol

Details on test material:

- Name of test material (as cited in study report): MRD-86-962
- Physical state: liquid
- Analytical purity: 100%
- Lot/batch No.: 1
- Storage condition of test material: room temperate

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hazelton Research Products, Inc. Denver, Pennsylvania
- Age at study initiation: 12 weeks
- Weight at study initiation: 2.25 to 3.06 kg
- Housing: Individual in suspended stainless steel cages
- Diet (e.g. ad libitum): Purina certified rabbit chow ad libitum
- Water (e.g. ad libitum): Automatic watering system (Elizabethtown watering company) ad libitum
- Acclimation period: 13 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-21
- Humidity (%): 40-60
- Photoperiod (hrs dark / hrs light):12/12


IN-LIFE DATES: From: June/July 1986 To: September 29-1986

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): 100%

Duration of treatment / exposure:

Single treatment

Observation period (in vivo):

14 days

Number of animals or in vitro replicates:

3/sex/group

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none


SCORING SYSTEM: Draize Scale

I. CONJUNCTIVAE

A. Redness (refers to palpebral and bulbar conjunctivae
excluding cornea and iris)
Vessels normal 0
Some vessels definitely injected 1
Diffuse, crimson red, individual vessels not easily discernible 2
Diffuse beefy red 3

Q. Chemosis
No swelling 0
Any swelling above normal (includes nictitating membrane) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half closed 3
Swelling with lids more than half closed 4

C. Discharge
No discharge 0
Any amount different from normal (does not include small amounts observed in inner canthus of normal animals) 1
Discharge with moistening of the lids and hairs just adjacent to lids
Discharge with moistening of the lids and hairs, and considerable area around eye 3

D. Necrosis or ulceration of palpebral and bulbar
conjunctivae or nictitating membranes

Not present 0*
Necrosis present N*
Ulceration present U*
Conjunctivae Score: (A + B + C) X 2 (maximum = 20)
* - Not included in Draize grading system

II. IRIS
A. Values
Normal 0
Markedly deepened folds, congestion, swelling, circumcorneal injection (any of these), iris still reacting to light (sluggish reaction is positive).1
No reaction to light, hemorrhage, gross destruction (any of these) 2
Iris Score: A X 5 (maximum = 10)

III. CORNEA

A. Opacity-degree of density (area most dense)
No opacity 0
Slight dulling of the normal luster +*
Scattered or diffuse areas of opacity, details of iris clearly visible 1
Easily discernible translucent area, details of iris slightly obscured.. 2
Nacreous areas, no details of iris visible, size of pupil barely discernible 3
Complete corneal opacity, iris not discernible 4

B. Area of cornea involved
Up to one quarter 1
Greater than one quarter, less than half 2
Greater than half, less than three quarters 3
Greater than three quarters .4

C. Stippling-area of pinpoint roughening
No stippling 0*
Up to one quarter 1*
Greater than one quarter, less than half 2*
Greater than half, less than three quarters 3*
Greater than three quarters 4*

D. Ulceration-absence of area of corneal epithelium
No ulceration P*
Up to one quarter :, 1*
Greater than one quarter, less than half 2*
Greater than half, less than three quarters 3*
Greater than three quarters 4*
Corneal Score: A X B X 5 (maximum = 80)
* - Not included in Draize grading system


TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #1

Time point:

other: 24 hour

Score:

ca. 23

Max. score:

110

Reversibility:

not fully reversible within: 24 hours

Results 2

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #2

Time point:

other: 24 hours

Score:

ca. 23

Max. score:

110

Reversibility:

not fully reversible within: 24 hours

Results 3

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #3

Time point:

other: 24 hours

Score:

ca. 19

Max. score:

110

Reversibility:

not fully reversible within: 24 hours

Results 4

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #4

Time point:

other: 24 hours

Score:

ca. 8

Max. score:

110

Reversibility:

not fully reversible within: 24 hours

Results 5

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #5

Time point:

other: 24 hours

Score:

ca. 23

Max. score:

110

Reversibility:

not fully reversible within: 24 hours

Results 6

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #6

Time point:

other: 24 hours

Score:

ca. 25

Max. score:

110

Reversibility:

not fully reversible within: 24 hours

Results 7

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #1

Time point:

other: 14 days

Score:

ca. 2

Max. score:

110

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: study terminated at 14 days, however trend of reversibility was observed

Results 8

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #2

Time point:

other: 14 days

Score:

ca. 0

Max. score:

110

Reversibility:

fully reversible

Results 9

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #3

Time point:

other: 14 days

Score:

ca. 0

Max. score:

110

Reversibility:

fully reversible

Results 10

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #4

Time point:

other: 14 days

Score:

ca. 2

Max. score:

110

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: study terminated at 14 days, however trend of reversibility was observed

Results 11

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #5

Time point:

other: 14 days

Score:

ca. 2

Max. score:

110

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: study terminated at 14 days, however trend of reversibility was observed

Results 12

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #6

Time point:

other: 14 days

Score:

ca. 0

Max. score:

110

Reversibility:

fully reversible

Results 13

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Results 14

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 4 days

Remarks on result:

positive indication of irritation

Results 15

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 10 days

Remarks:

Score at 10 days was 1

Remarks on result:

positive indication of irritation

Results 16

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks:

score at 14 days: 1

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Ocular instillation of MRD-86-962 elicited conjunctival, corneal and iridial responses in all animals.
Conjunctival responses included redness, chemosis, clear/white discharge and conjunctival ulceration. Redness was noted in all animals from the 1 Hour observation through the Day 10 observation. The incidence of redness decreased after these observations and three animals were noted with redness at the Day 14 observation. Chemosis was noted in all animals from the 1 Hour observation through the 48 Hour observation. The incidence of chemosis declined after these observations and chemosis was not noted at the Day 14 observation. Clear and/or white discharge was noted in all animals at the 1 and 4 Hour observations. The incidence of discharge decreased after these observations and no discharge was noted by the Day 4 observation. Conjunctival ulceration was noted in five animals during the study.
Iridial responses were noted in all animals during the study with varying incidences at the different observation intervals. Iridial responses were not noted after the Day 7 observation.
Corneal responses included opacity, stippling and corneal ulceration. Corneal opacity was noted in five animals, stippling was noted in five animals and corneal ulceration was noted in all animals during the study. All animals were clear of corneal responses by Day 7.
Other observations noted during the study included dye retention of the nictitating membrane and conjunctiva, and conjunctival blistering.
Ocular irritation was most prominent from the 1 Hour through the Day 4 observations where the total Draize score ranged from 4 to 25.

Any other information on results incl. tables

Animal	Effect	24 hrs	48 hrs	72 hrs	24-72hr avg	4 days	7 days	10 days	14 days
1	Cornea	4	4	3	3.67	1	0	0	0
	Iris	1	1	1	1.00	0	0	0	0
	Redness	3	3	3	3.00	3	2	1	1
	Chemosis	3	3	3	3.00	1	1	1	0
2	Cornea	4	2	0	2.00	0	0	0	0
	Iris	1	1	0	0.67	0	0	0	0
	Redness	3	3	3	3.00	3	1	1	0
	Chemosis	3	3	2	2.67	1	1	0	0
3	Cornea	3	2	0	1.67	0	0	0	0
	Iris	1	1	1	1.00	0	0	0	0
	Redness	3	3	3	3.00	3	1	1	0
	Chemosis	2	1	1	1.33	1	1	0	0
4	Cornea	0	0	0	0.00	0	0	0	0
	Iris	1	1	0	0.67	0	0	0	0
	Redness	3	3	3	3.00	3	1	1	1
	Chemosis	1	1	0	0.67	1	0	0	0
5	Cornea	4	3	2	3.00	0	0	0	0
	Iris	1	1	1	1.00	1	1	0	0
	Redness	3	3	3	3.00	3	2	1	1
	Chemosis	3	2	1	2.00	1	1	0	0
6	Cornea	2	1	0	1.00	0	0	0	0
	Iris	1	0	0	0.33	0	0	0	0
	Redness	3	3	2	2.67	2	2	1	0
	Chemosis	4	2	1	2.33	0	0	0	0
6-animal averages:   Cornea Iris Redness Chemosis					1.89	6 animals not fully reversed	6 animals not fully reversed	6 animals not fully reversed	3 animals not fully reversed

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Remarks:

Causes serious eye irritation Criteria used for interpretation of results: other: CLP (EC 1272/2008)

Executive summary:

The results demonstrate a trend in reversibility; however, the study was ended at the day 14 instead of day 21 and full reversibility may have been observed at day 21.