Propan-2-ol

Endpoint summary

Description of key information

Skin irritation studies on isopropyl alcohol in rabbits and guinea pigs have demonstrated that the compound is not a skin irritant.

Eye irritation studies on isopropyl alcohol in rabbits have demonstrated that the compound is an eye irritant.  

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study without detailed documentation.

Qualifier:

no guideline followed

Principles of method if other than guideline:

This test followed the revised Federal Hazardous Substances Act (FHSA) procedure that had been proposed by the FDA (Edwards, 1972), with a 4-hour rather than 24-hour exposure.

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

No details provided.

Type of coverage:

occlusive

Preparation of test site:

other: intact and abraded skin

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No details provided.

Duration of treatment / exposure:

4 hours

Observation period:

at 4, 24, and 48 hours

Number of animals:

No details provided.

Details on study design:

TEST SITE
- Area of exposure: 2 intact sites and 2 abraded sites per animal
- % coverage: not reported
- Type of wrap if used: patch (unspecified)


REMOVAL OF TEST SUBSTANCE
- Washing (if done): not reported
- Time after start of exposure: not reported


SCORING SYSTEM: see below

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

Observations were not made at 72 hours, but as scores for all animals were 0 at 4,24 and 48 hours, it is assumed that the 24/48/72 hour score would be 0. It is assumed that at least three animals were used.

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

Observations were not made at 72 hours, but as scores for all animals were 0 at 4,24 and 48 hours, it is assumed that the 24/48/72 hour score would be 0. It is assumed that at least three animals were used.

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

Observations were not made at 72 hours, but as scores for all animals were 0 at 4,24 and 48 hours, it is assumed that the 24/48/72 hour score would be 0. It is assumed that at least three animals were used.

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

Observations were not made at 72 hours, but as scores for all animals were 0 at 4,24 and 48 hours, it is assumed that the 24/48/72 hour score would be 0. It is assumed that at least three animals were used.

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

Observations were not made at 72 hours, but as scores for all animals were 0 at 4,24 and 48 hours, it is assumed that the 24/48/72 hour score would be 0. It is assumed that at least three animals were used.

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

Observations were not made at 72 hours, but as scores for all animals were 0 at 4,24 and 48 hours, it is assumed that the 24/48/72 hour score would be 0. It is assumed that at least three animals were used.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 4, 24, 48 hr

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: no irritation observed

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 4, 24, 48 hr

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: no irritation observed

Irritation parameter:

other: tissue destruction

Basis:

mean

Time point:

other: 4, 24, 48 hr

Score:

0

Max. score:

6

Reversibility:

other: not applicable

Remarks on result:

other: no corrosion observed in any (0) of the 6 sites tested

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: CLP (EC 1278/2008)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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

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

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

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

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

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

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

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

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

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

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

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #2

Time point:

other: 14 days

Score:

ca. 0

Max. score:

110

Reversibility:

fully reversible

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #3

Time point:

other: 14 days

Score:

ca. 0

Max. score:

110

Reversibility:

fully reversible

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

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

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #6

Time point:

other: 14 days

Score:

ca. 0

Max. score:

110

Reversibility:

fully reversible

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

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

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

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation: 

Isopropyl alcohol did not induce dermal irritation in intact and abraded skin of rabbits or guinea pigs after a single 4-hour occlusive application. A skin irritation study on isopropyl alcohol has been performed in accordance with revised Federal Hazardous Substances Act (FHSA) procedure that had been proposed by the FDA (Nixon et al., 1975).  In this study, rabbits (strain and number of animals not reported) and Hartley guinea pigs (number of animals not reported) were exposed to isopropyl alcohol (vehicle not reported) on the intact and abraded sites (total number of sites tested was 6 for intact skin and 6 for abraded skin) under occlusive conditions.  Animals were exposed to the test compound for 4 hours and observations were recorded at 4, 24, and 48 hours after removal of the patch (washing not reported).   Skin reactions were scored according to a prescribed numerical system (Edwards, 1972) and the primary irritation index (PII) was calculated by averaging the scores for all test sites.  In addition, tissue destruction was presented as the number of sites that showed tissue destruction or a reaction grade >4.0, excluding actual abrasion, at any grading time and as a function of the total number of sites tested. 

In both rabbits and guinea pigs, the mean score for irritant response was 0 for both intact and abraded skin. The PII was 0 and the tissue destruction fraction was 0 out of 6, whether the skin was intact or abraded. Based on the results of this study, isopropyl alcohol is not a skin irritant. Isopropyl alcohol is not classified as a skin irritant according to the CLP classification criteria. 

Eye Irritation: 

Eye irritation studies on isopropyl alcohol in rabbits have demonstrated that the compound is an eye irritant. 

An eye irritation study on isopropyl alcohol has been performed in rabbits (Plutnick, 1986).  In this study, 0.1 mL of undiluted isopropyl alcohol was instilled into one conjunctival sac of each of 6 New Zealand White rabbits (3/sex).  Ocular changes were assessed 1, 4, 24, 48, 72 hours and 4, 7, 10, and 14 days after treatment, and scoring was performed according to the guideline methods with additional parameters assessed for the conjunctivae and cornea.  Instillation of isopropyl alcohol caused conjunctival, corneal, and iridial responses in all animals. Conjunctival responses, including redness, chemosis, and clear/white discharge were observed in all animals 1 hour after treatment. Specifically, redness was noted in all animals from 1 hour after treatment through to Day 10. Although the incidence of redness was observed to be decreased at study termination (Day 14), redness was still noted in 3 animals. Chemosis was noted in all animals from 1 hour through to 48 hours after treatment. The incidence of chemosis subsequently decreased and chemosis was not noted on Day 14. Clear and/or white discharge was noted in all animals at the 1- and 4-hour observations and was fully reversed by Day 4. Conjunctival ulceration was noted in 5 animals during the study. Iridial responses were noted in all animals during the study and were reversed by Day 7. Corneal responses including, opacity and stippling, were observed in 5 animals. Corneal ulceration was noted in all animals. Corneal responses in all animals were reversed 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 1 hour after treatment through to Day 4. The total Draize score ranged from 4 to 25. Three of the 6 rabbits displayed conjunctival redness on Day 14. Under the conditions of this study, isopropyl alcohol was considered to be irritating to rabbit eyes. 

According to CLP classification criteria and in accordance with Annex VI of Regulation (EC) No 1272/2008, isopropyl alcohol is classified as category 2 (causes serious eye irritation).

In another eye irritation study conducted with rabbits (Eye Irritation: Reference chemicals data bank, 1998), undiluted isopropyl alcohol was instilled into 4 rabbits (strain not reported), and ocular changes were assessed 24, 48, 72 hours and 7 and 10 days after treatment. Ocular changes were scored against the maximum average scoring system of Draize (1944). The modified maximum average scored at 1 day was 30.5 out of a possible score of 110. Effects were fully reversed in 10 days. Therefore, isopropyl alcohol is irritating to rabbit eyes. 

According to CLP classification criteria and in accordance with Annex VI of Regulation (EC) No 1272/2008, isopropyl alcohol is classified as category 2 (causes serious eye irritation).

IPA has been tested for in vitro eye corrosion in a published study conducted according to OECD Test Guideline 491 (2015), GLP compliance not stated (Abo et. al., 2018). When tested with using saline as a solvent, the cell viability was >70% at 5% and 0.05% IPA, with the conclusion that the substance is not an eye irritant. This result is ignored, as saline is not an appropriate solvent for highly volatile substances (OECD Test Guideline 491, 2020, citing this publication). When mineral oil was used as a solvent, the cell viability was 6.9% at 5% test substance, but 97.8% at 0.05% IPA, considered by the authors to show that IPA was an eye irritant, but indicating that no GHS prediction can be made from this study according to the guideline. No further in vitro testing is required as reliable in vivo data are available.

Justification for classification or non-classification

Skin irritation: The substance does not meet the criteria for classification and labelling for skin irritation according to Regulation (EC) No. 1272/2008.

Eye irritation: the substance does meet the criteria for classification and labelling for this endpoint (Category 2: causes serious eye irritation) in accordance with Annex VI of Regulation (EC) No. 1272/2008.