Oxydipropanol

Endpoint summary

Description of key information

Two studies with human volunteers and one guideline animal study all indicate that dipropylene glycol does not have a skin irritating potential.
The substance was also found to be not irritating to eye in a GLP-compliant study with rabbits. 

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Qualifier:

according to guideline

Guideline:

EPA OPP 81-5 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: bred in the laboratory colony (Branchville)
- Age at study initiation: approximately 16 weeks
- Weight at study initiation: 2.0 to 2.3 kilograms
- Housing: housed individually under standard laboratory conditions in the study room
- Diet (e.g. ad libitum): Blue Seal Rabbit Feed, ID 1661 JJA, supplemented with oats if necessary
- Water (e.g. ad libitum): potable municipal water ad libitum
- Acclimation period: five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 68-74ºF
- Humidity (%): 35-65%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours on 12 hours off cycle

Type of coverage:

occlusive

Preparation of test site:

other: clipped closely

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

A dose of 0.5 ml of the test substance was applied per application site.

Duration of treatment / exposure:

The exposure was maintained for 4 hours.

Observation period:

Readings were made 30 to 60 min after cleaning the skin at approximately 4 hr, and at the end of 24, 48 and 72 hours after patch removal.

Number of animals:

6 animals; 3 male, 3 female

Details on study design:

On the day before dosing, the dorsal surface around the test site of each rabbit was clipped closely. The skin was gently wiped with clean moistened paper towel. Any animal having a severe reaction two hours after clipping was not used. One site on each animal was selected for testing. Test substance was introduced under a gauze pad approximately 6 cmm secured by hypo-allergenic adhesive tape. The trunk of the rabbit was then wrapped with non-irritating perforated plastic sheeting fastened at each end with masking tape in order to prevent displacement of the test substance. At the end of the 4 hour exposure period, the plastic sheeting and gauze were removed and the skin was wiped with clean moistened paper towel to remove any test substance still remaining. 30 - 60 minutes after cleaning the skin the reactions at each site were scored for erythema and edema using the modification of the method of Draize.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects at 24 hr and thereafter

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects at 24 hr and thereafter

Irritant / corrosive response data:

45 minutes after patch removal there was no irritation except for one site (1/6) which showed very slight erythema. At 24 hours all test areas appeared normal and remained normal throughout the duration of the study. There was no evidence of any corrosive effect.

Other effects:

No evidence of systemic pharmacotoxic effect was obeserved. The rabbits did not show signs of discomfort such as vocalization or excessive struggling upon application of the test substance.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Qualifier:

according to guideline

Guideline:

EPA OPP 81-4 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: bred in the laboratory colony (Branchville)
- Age at study initiation: approximately 12 weeks
- Weight at study initiation: 2.0 to 2.1 kilograms
- Housing: housed individually under standard laboratory conditions in the study room
- Diet (e.g. ad libitum): Blue Seal Rabbit Feed, ID 1053 KLA, or equivalent, supplemented with oats if necessary
- Water (e.g. ad libitum): potable municipal water ad libitum
- Acclimation period: at least five days


ENVIRONMENTAL CONDITIONS
- Temperature: 68-74ºF
- Humidity (%): 35-65%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours on/12 hours off cycle

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

One eye of each animal was dosed with 0.1 ml of the test substance, while the other eye served as an untreated control.

Duration of treatment / exposure:

The eyes were not washed after instillation of the test substance unless, one hour later, the accumulation of debris/discharge interfered with eye examination and this was noted in the observations.

Observation period (in vivo):

All treated and control eyes were graded and scored at approximatly 1, 24, 48 and 72 hours. If positive ocular scores persisted at 72 hours, those eyes were re-examined on Day 4 using the same criteria and every three or four days thereafter, until the irritation became "not positive" or the healing was considered likely to be very prolonged.

Number of animals or in vitro replicates:

6 animals; 3 male, 3 female

Details on study design:

Twenty-four hours prior to dosing, both eyes of each rabbit were examined using a hand held ophthalmoscope and then by an ultraviolet light to detect fluorscein retentin. For this procedure one drop of Fluorescein Sodium Ophthalmic Solution USP was dropped onto the cornea and 10-15 seconds later it was washed away with tap water. The eyes were examined for dye retention. Only animals free of apparent ocular defects were selected for this study. At the time of dosing, the animal was held quiet and the lower lid was everted from the eyeball to form a cup into which the test substance was placed at the specified dose. The eyelids were then gently held together for one second. The eyes were not washed after instillation of the test substance unless, one hour later, the accumulation of debris/discharge interfered with eye examination and this was noted in the observations. Any reaction to the instillation of the test substance was noted. If any rabbit showed evidence of severe pain, the protocol required use of a local anesthetic, euthanasia of that animal, or termination of the test.
All treated and control eyes were graded and scored at approximatly 1, 24, 48 and 72 hours using the criteria established in the 'Illustrated Guide for Grading Eye Irritation by Hazardous Substances" which uses a modified Draize scoring method. A hand held ophthalmoscope or slit lamp was used to facilitate examination. In addition, at approximatly 24 and 72 hours, both eyes were examined using the fluorescein method as perviously described.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects at 24 h and thereafter

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effects at 24 h and thereafter

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: no effects at 24 hr and thereafter

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects at 24 hr and thereafter

Irritant / corrosive response data:

At one hour there was very slight irritation characterized by conjunctival redness (grade 1) in all eyes with two also showing chemosis (Grade 1). At 24 hours all eyes appeared normal and remained normal through 72 hours. At no time was there any corneal involvement and there was no corrosive effect on the eye.

Other effects:

No evidence of any systemic effect was observed. Immediately following application of the test substance to the dosed eyes there was no evidence of pain, such as prolonged blepharospasm, excessive struggling of vocalization.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

One GLP-compliant study with rabbits, performed in accordance with EPA OPP 81-5 (Acute Dermal Irritation) guideline (Cosmopolitan Safety Evaluation, Inc., 1995) was available for assessment. A dose of 0.5 ml of the test substance was applied under occlusion to a clipped test site of 6 (3 males, 3 females) rabbits for 4 hours. 45 minutes after patch removal no irritation was observed except for one site (1/6) which showed very slight erythema. At 24 hours all test areas appeared normal and remained normal throughout the duration of the study. Mean (24 + 48 + 72 h) scores were 0 for both erythema and oedema.

Besides animal studies, 2 human volunteer studies were available for assessment. The first one, a 24-h semi-occluded patch study, was conducted to compare the skin irritancy potential of several test articles, including dipropylene glycol (Hill Top Research, Inc., 1995). The test substance was prepared as a 25% solution in distilled water and 0.2 ml of the solution was placed on the patch pad and applied on the paraspinal region of the back of 33 subjects. The results were compared with 2 negative controls (water and USP oil) and a positive control (0.5% sodium lauryl sulfate). All skin sites were scored prior to the application, 30 min after the removal of the 24 h application and again 24 h following patch removal.

Twenty-four subjects did not show any signs of skin irritation throughout the test period. Two subjects were clear at the 30 min evaluation, however, the response increased to mild erythema at the 24 h evaluation. Nine subjects exhibited mild to moderate erythema at the 30 min evaluation. Seven of these subjects responses were resolved by the 24 h evaluation, the remaining two subjects still exhibited mild erythema at the 24 h evaluation.

 

In the second study (Consumer Product Testing Co., 1997), a 14-day cumulative irritation test, approximately 0.2 ml of the test material was applied neat and as 50% solution under occlusive dressing to the upper back of 26 human volunteers. The test material was applied Monday through Friday. Patches applied on Friday remained in place until the following Monday for a total of 14 days of skin contact. Only one of the subjects showed mild erythema during the first 4 days of the study which was resolved for the rest of the test period upon treatment with neat dipropylene glycol. The other 25 subjects did not show any signs of skin irritation at any time during the test.

In conclusion, based on both human and animal data, dipropylene glycol is considered not to have skin irritating properties.

Eye irritation

One GLP-compliant eye irritation study with rabbits, performed in accordance with EPA OPP 81-4 (Acute Eye Irritation) guideline (Cosmopolitan Safety Evaluation, Inc., 1995), was available for assessment.

6 animals (3 males, 3 females) were used. At one hour there was very slight irritation characterized by conjunctival redness (grade 1) in all eyes with two also showing chemosis (Grade 1). At 24 hours all eyes appeared normal and remained normal through 72 hours. At no time was there any corneal involvement and there was no corrosive effect on the eye. No evidence of any systemic effect was observed. Immediately following application of the test substance to the dosed eyes there was no evidence of pain, such as prolonged blepharospasm, excessive struggling of vocalization. Based on the results, it is concluded that dipropylene glycol is not irritating to rabbit eyes.

Justification for classification or non-classification

Based on the absence of skin and eye irritating effects in the available animal and human volunteers study, the substance does not have to be classified according to Directive 67/548/EEC and EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.