1-propoxypropan-2-ol

Endpoint summary

Description of key information

Several non-GLP studies equivalent to OECD guidelines 404 and 405 are available for propylene glycol n-propyl ether (PnP).

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:

1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: non-GLP study equivalent to OECD guideline 404

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

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

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

6 (3 males & 3 females)

Details on study design:

TEST SITE
- Type of wrap if used: gauze patch loosely covered with impervious sheeting

REMOVAL OF TEST SUBSTANCE
- Washing (if done): excess sample was removed after contact
- Time after start of exposure: 4h

SCORING SYSTEM: skin reaction is scored by the method of Draize (see table below)

Irritation parameter:

erythema score

Basis:

mean

Remarks:

over all animals

Time point:

other: 24, 48 and 72 hours

Score:

0.9

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

mean

Remarks:

over all animals

Time point:

other: 24, 48 and 72 hours

Score:

0.4

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

Minor to moderate erythema on 4 of 6 rabbits, minor edema on 3 from 0.5 ml; no irritation, except desquamation, after 7 days

Other effects:

none

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The application of 0.5 ml PROPASOL Solvent P to occluded rabbit skin resulted in mean irritation scores of 0.9 (erythema) and 0.4 (edema); fully reversible within 7 days. Therefore, it can be concluded that PROPASOL Solvent P is not irritating according to EU classification.

Executive summary:

Three male and three female New Zealand White rabbits were dosed with 0.5 ml PROPASOL Solvent P. The dose was applied to the clipped, intact skin under a gauze patch and was loosely covered with impervious sheeting. The test material was applied to each of 6 rabbits, which were restrained for the 4 -hour contact period. Excess sample was removed after contact. Skin reaction was scored by the method of Draize at one hour, one day, 2 days, 3 days, 7 days, 10 days and 14 days after dosing. The 4-hour application of PROPASOL Solvent P to occluded rabbit skin resulted in minor to moderate erythema on 4 of 6 rabbits and minor edema on 3. After 7 days, half of the rabbits developed desquamation, but no other irritation was evident. By 14 days there was desquamation on only one animal.

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: non-GLP study equivalent to OECD guideline 405

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml, 0.01 ml and 0.005 ml
- Concentration (if solution): pure substance (100%)

Duration of treatment / exposure:

single application

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

18 (3 males & 3 females per dose level)

Details on study design:

SCORING SYSTEM: the eyes were scored by the system below at one hour, 4 hours, 1 day, 2 days, 3 days, 7 days, 14 days and 21 days.

TOOL USED TO ASSESS SCORE: fluorescein (to determine corneal injury)

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

over all animals

Time point:

other: 24, 48 and 72 hours

Score:

0.9

Max. score:

1

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: 5 out of 6 animals had an average score of 1

Irritation parameter:

iris score

Basis:

mean

Remarks:

over all animals

Time point:

other: 24, 48 and 72 hours

Score:

0.7

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

over all animals

Time point:

other: 24, 48 and 72 hours

Score:

0.9

Max. score:

1

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

over all animals

Time point:

other: 24, 48 and 72 hours

Score:

0.8

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

0.1 ml: minor diffuse corneal injury (opacity), iritis and moderate to severe conjunctival irritation in 6/6 animals; after 7 days: 5/6 appeared normal, 1/6 with persistent corneal vascularization
Microscopically, 6.6 exhibited minimal conjunctival injury characterized by edema, inflammation and perivascular lymphoid infiltrates. These lesions were associated with the corneal limbus. 1/6 had vacuolation of the corneal epithelium.

0.01 ml: diffuse corneal opacity, iritis and moderate conjunctival irritation in 6/6 animals; complete healing with 3 days in 1/6, within 7days in 6/6
Microscopically, 2/6 had mild to moderate conjunctival edema and inflammation in the limbus region. 4/6 had no remarkable histologic lesions.

0.005 ml: minor diffuse corneal injury, iritis and minor to moderate conjunctival irritation in 6/6 animals; complete healing within 3 days in 1/6 and within 7 days in 6/6
Microscopically, 0/6 exhibited significant lesions.

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

PROPASOL Solvent P may cause moderate eye irritation and should be classified as eye irritant category 2 according to EU CLP criteria.

Executive summary:

Eighteen New Zealand White rabbits (9/sex) were divided into three groups and were exposed to a single dose of 0.005 ml, 0.01 ml, and 0.01 ml of PROPASOL Solvent P inserted into the conjunctival sac (0.1 ml dose) or applied directly to the cornea (0.01 ml and 0.005 ml) of one of their eyes. The eyelids were held together for one second. Six eyes were dosed per test volume. The animals in the low and intermediate exposure groups were held for observation for one week and then sacrificed. The animals in the high dose exposure group were held for three weeks before sacrifice. The eyes were scored by the system described above at one hour, 4 hours, one day, 2 days, 3 days, 7 days, 14 days and 21 days after dosing. Fluorescein staining was used to determine corneal injury before dosing and at readings after one day. The eyes were collected from all rabbits after euthanasia for pathologic evaluation.

Instillation of 0.1 ml PROPASOL Solvent P into rabbit eyes resulted in minor diffuse corneal injury (opacity) in 6 of 6 animals. Iritis was apparent in 6 animals and moderate to severe conjunctival irritation developed in all 6 animals. After 7 days, 5 rabbits exhibited a normal appearance, but one animal developed corneal vascularization which persisted through 21 days.

After instillation of 0.01 ml, 6 of 6 animals developed minir diffuse corneal opacity. There was iritis in 6 rabbits. Moderate conjunctival irritation appeared in all 6 animals. There was complete healing in one animal within 3 days. Irritation subsided in the other 5 animals by 7 days.

A volume of 0.005 ml produced minor diffuse corneal injury, iritis and minor to moderate conjunctival irritation in 6 rabbits. One animal was healed at 3 days and all appeared normal after 7 days.

Microscopically, eyes dosed with 0.1 ml exhibited minimal conjunctival injury characterized by edema, inflammation abd perivascular lymphoid infiltreates. These lesions were associated with the corneal limbus. One eye had vacuolation of the corneal epithelium. Two middle dose (0.01 ml) eyes had mild to moderate conjunctival edema and inflammation in the limbus region. Four eyes had no remarkable histologic lesions after the 0.01 ml dose. None of 6 eyes receiving 0.005 ml of PROPASOL Solvent P exhibited significant microscopic lesions.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The undiluted material was only very slightly irritating to rabbit skin and all effects were fully resersible within 7 days.

Only mild eye irritation was observed with PnP when applied undiluted to rabbits eyes, all effects were fully resersible within the observation period. There are no studies available for respiratory irritation.

Justification for selection of skin irritation / corrosion endpoint:
reliable study

Justification for selection of eye irritation endpoint:
reliable study

Effects on eye irritation: irritating

Justification for classification or non-classification

Propylene Glycol n-Propyl Ether is not irritating to skin according to EU classification criteria based on mean irritation scores < 1 for erythema and edema with all effects being fully reversible within 7 days.

Propylene Glycol n-Propyl Ether is irritating to eyes according to EU CLP classification criteria based on mean irritation scores of 1 for cornea opacity in 5 out of 6 animals with all effects being fully reversible within 14 days. According to the DSD criteria it does not need to be classified for eye irritation.

Propylene Glycol n-Propyl Ether is not expected to be irritating to the respiratory system as there were minimal to no effects noted in the eye and skin irritation studies.