2-isopropoxyethanol

Endpoint summary

Description of key information

Irritating to skin

Irritating to eyes

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:

1995

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Remarks:

Study reported in sufficient detail to be able to judge it as reliable in contributing to the understanding of the skin irritancy properties of this substance. No individual animal data available. Not to GLP

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ‘Elevage Scientifique des Dombes’ (Ain, France)
- Housing: housed individually.
- Diet (e.g. ad libitum): Food available ad libitum.
- Water: available ad libitum


ENVIRONMENTAL CONDITIONS
- Humidity (%): 55%+/-5
- Photoperiod (hrs dark / hrs light): 12hr light/dark cycle.

Type of coverage:

occlusive

Preparation of test site:

other: shaved for main test. Abraded and non abraded skin used for second test to Draize protocol

Vehicle:

unchanged (no vehicle)

Controls:

other: a number of other glycol ethers were examined in the study.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5ml
- Concentration (if solution): 100%:

Duration of treatment / exposure:

4 hours (24 for Draize experiment)

Observation period:

3 weeks

Number of animals:

3 for EC method and 6 in Draize protocol experiment

Details on study design:

TEST SITE
- Area of exposure: no data
- Type of wrap if used: no data

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data

SCORING SYSTEM: Draize (0-4 for erythema and odema) but using the EU assessment criteria. Subsequent test to Draize test protocol used primary irritation index.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 and 72hrs

Score:

4.8

Max. score:

8

Remarks on result:

other: Sum of 24 and 72 hour observations for both abraded and non abraded skin

Remarks:

Data for individual animals not available in published report

Irritant / corrosive response data:

Main test: irritating
Draize protocol test: severely irritating.

Other effects:

none reported

Primary irritation index result would suggest severe erythema and oedema in some animals.

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Data suggests that the substance is irritating in its own right, without taking into account persistence. Whilst individual animal data is not available, a result of >4 for the PII strongly suggests that the criteria for classification will be met. This was also the conclusions of the authors.

Executive summary:

In a reasonably well reported study in rabbits carried out to an EU guideline for irritancy testing, 2 -isopropoxyethanol showed moderate signs of irritation to the skin. The reported primary irritation index (which resulted from a study using abraded and intact skin) was 4.8, which suggested that the animals produced reactions of Draize levels 2 -3 (well defined to marked erythema and slight to moderate odema). Overall, this study indicates that the substance is meets the criteria for classification as a skin irritant in the EU based on the criteria of the CLP regulation.

Synopsis:

Irritating

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin irritation

In a reasonably well reported study in rabbits carried out to an EU guideline for irritancy testing, 2 -isopropoxyethanol showed moderate signs of irritation to the skin. The reported primary irritation index (which resulted from a study using abraded and intact skin) was 4.8, which suggested that the animals produced reactions of Draize levels 2 -3 (well defined to marked erythema and slight to moderate odema). An older study, that cannot be rated for reliability used 2 -isopropoxyethanol applied uncovered to the skin of rabbits for 24 hours. The material did not show a irritation potential under the conditions of this study. Overall, this data indicates that the substance meets the criteria for classification as a skin irritant in the EU based on the criteria of the CLP regulation.

Eye irritation

There is only one, old study available for 2 -isopropoxy ethanol. In this study, instillation of the substance into rabbits eye induced marked conjunctival irritation, marked corneal injury and some iritis. These effects were reversible within approximately 7 days. Whilst old and not to guideline and not reported in a form that allows exact comparison with the classification guidelines, the study is regarded as reliable.

To support the results from the study above and provide a higher level of confidence in the conclusions, data is also drawn from the isomer n-propoxyethanol, which is used as a source substance. Three studies are available. Some of these are also old but also reliable.

In a study using 2 -(propyloxy)ethanol, rabbit eyes were instilled with 0.1ml of the test substance leaving the second eye untreated as control. The eyes were evaluated within 1 min, and 1, 24, 48hr and 14 days after treatment and ocular lesions graded according to Draize guidelines. Numeric results were not reported. The test substance produced a moderate to strong eye irritation.

In a second study, two drops of undiluted test material was applied to the eyes of a rabbit. One eye was washed within 30 seconds of administration and the other was unwashed. Obsevations were made immediately, 1, 24 and 48 hours, and 7 days. In the unwashed eye, moderate conjunctival swelling, corneal damage, slight iritis were observed and did not subside in 1 week. In the washed eye, moderate conjunctival swelling, corneal damage not as severe as unwashed eye, slight iritis were observed and did not subsided in 1 week. Internal effects in washed and unwashed eye ranged from a score of 1-3 out of a maximum score of 6, reflecting no response to slight, just perceptible.

In a third study, the ocular irritancy of the compound was determined using a Standardized test administration of' one drop of liquid to the conjunctival sacs of 6 rabbit eyes, three of which were promptly washed. The compound was moderate to strong eye irritant causing slight to severe erythema and slight to moderate edema of the conjunctivae, iritis and staining of adnexae and cornea. Some degree of corneal opacity was seen in all eyes tested . All signs resolved by 14 days. Prompt irritation had a slight palliative effect.  

Further weight of evidence can be gathered from a GLP study performed according to OECD guideline 405 where rabbits were instilled with 2 -butoxyethanol. Animals were observed for 21 days. Eye washing was performed about 24 hours after treatmnent, before the 24 hour reading. This practice is optional in the guideline but is considered more representative of human exposure, where lachrymation will create a washing action. One animal exhibited a slight corneal opacity reversible in 21 days. Signs of a slight iris injury was described, reversible in 7 days. A medium to severe irritation of the conjunctivae was also observed and was reversible in 21 days. According to criteria for assessment of ocular lesions, 2 -butoxyethanol can be considered as an eye irritant category 2.

Respiratory irritation

There is no data available on respiratory irritation.

Justification for classification or non-classification

Detailed quantitative data is not available for the eye and skin irritancy properties of the substance isopropoxyethanol. However, from the available semi-quantitative and qualitative information on both this substance and its isomer n-propoxyethanol, along with further weight of evidence from the substance 2 -butoxyethanol for eye irritation, it can be concluded that isopropoxyethanol should be classified category 2 for both skin and eye irritation (H315, H319 under regulation 1272/2008.)