Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Skin irritation study in rabbits and eye irritation studies in 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
Study period:
September 13, 1994 - March 3, 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
Qualifier:
according to guideline
Guideline:
other: MAFF Primary Dermal irritation
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Rabbits were obtained from Hazleton Research Products, Inc. (Kalamazoo, MI) and weighed 2.01 - 2.38 kg upon arrival. They were housed in a room maintained at 40-60% relative humidity, 19 +/- 3 degrees C, and a 12 hour light/12 hour dark cycle. Room air exchanged 15 times/hour. Four ounces of Purina Certified Rabbit Chow #5322 (Purina Mills Inc., St. Louis, MO) were provided daily and tap water was provided ad libitum. Animals were acclimated for at least two weeks before use.
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
24, 48 and 72 hours
Number of animals:
6 (3/sex)
Details on study design:
The test material (0.5 ml) was applied to a Hill Top Chamber (25 mm), which was affixed with an elastic rabbit jacket to back skin (10 cm x 10 cm) that had been clipped free of fur the day the previous day. The jacket and chamber were removed four hours later, and the site was wiped with a damp, disposable towel. The application sites were graded for erythema and edema within 30 min, and 24, 48 and 72 hours after removal of the test material on Days 7 - 15. Animals were weighed on the day of treatment and at study termination.
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean (male)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean (male)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean (male)
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #4
Remarks:
mean (female)
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: This female rabbit had severe erythema and gradually diminishing edema for the remainder of the study. The effects were not considered to be related to administartion of the test material since there was an error during application of the test material.
Irritation parameter:
erythema score
Basis:
animal #5
Remarks:
mean (female)
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #6
Remarks:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: day 7
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean (male)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean (male)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean (male)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #4
Remarks:
mean (female)
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: This female rabbit had severe erythema and gradually diminishing edema for the remainder of the study. The effects were not considered to be related to administartion of the test material since there was an error during application of the test material.
Irritation parameter:
edema score
Basis:
animal #5
Remarks:
mean (female)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #6
Remarks:
mean (female)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
One female rabbit had severe erythema and gradually diminishing edema for the remainder of the study. The effects were not considered to be related to administration of the test material since there was an error in applying the material.

For the remaining 5 rabbits, very slight erythema (Grade 1) was observed in two females within 30 minutes and two females and one male at 24 and 48 hours. This resolved by Day 7. No edema was observed in these rabbits.

Very slight erythema (Grade 1) was
Other effects:
There was no effect on body weight.

The female rabbit that had severe erythema and gradually diminishing edema for the remainder of the study should be excluded from the study. The effects were not considered to be related to administartion of the test material since there was an error during application of the test material.

Interpretation of results:
not classified
Conclusions:
Based on the results, dipropylene glycoln-propyl ether will not be classified as irritating.
Executive summary:

Dipropylene glycol n-propyl ether (DpnP, purity 99.32% by weight) was evaluated for primary dermal irritaion. Aliquots of 0.5 ml of DPnP were applied for four hours to the intact skin on the back of six New Zealand White rabbits. Very slight erythema was observed on two of the six rabbits within 30 minutes of test material removal. Three of the six rabbits at 24 and 48 hours had very slight erythema. Very slight erythema was present on one of the six rabbits 72 hours after test material removal which was resolved by test day 7.

One of the rabbits patch was inadvertently caught under the tape and was held very tightly in place for the four hour exposure. As a result of this error in application technique, the rabbit had severe erythema and gradually diminishing edema for the remainder of the study, neither of which were interpreted to be compond related. The test was terminated 14 days after test material removal. Dermal application of 0.5 ml dipropylene glycol n-propyl ether had no effect on body weight.

Based on the results of the study, dipropylene glycol n-propyl ether will not be classified as irritating.

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:
December 6, 1994 - March 3, 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: MAFF Primary Eye Irritation
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Rabbits were obtained from Hazleton Research Products, Inc. (Kalamazoo, MI) and weighed 2.57 - 2.79 kg at the start of the study. They were housed individually in a room maintained at 40-60% relative humidity, 19 +/- 3 degrees C, and a 12 hour light/12 hour dark cycle. Room air was exchanged 15 times/hour. Four ounces of Purina Certified Rabbit Chow #5322 (Purina Mills Inc., St. Louis, MO) were provided daily and tap water was provided ad libitum. Animals were acclimated for at least two weeks before use.
Vehicle:
unchanged (no vehicle)
Controls:
other: contralateral eye
Amount / concentration applied:
0.1 g
Duration of treatment / exposure:
not applicable
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
6 (3/sex)
Details on study design:
The day prior to exposure to test material, eyes were examined with 5% aqueous fluorescein and determined to be free of defects or irritation. Test material was instilled into the conjunctival sac of the right eye of each rabbit. The left eye was untreated and served as a control. Eyes were not washed after treatment. The behaviour of each rabbit was observed immediately after exposure for pain or discomfort. Both eyes were examined with a penlight 1, 24, 48 and 72 hours and 7 days after exposure for conjunctival redness and chemosis, discharge, corneal opacity and reddening of the iris. Rabbits were weighed on the day of exposure and study termination.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
over all male animals
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 8 days
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
over all female animals
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 8 days
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
over all animals
Time point:
24/48/72 h
Score:
0.6
Max. score:
1
Reversibility:
fully reversible within: 8 days
Irritation parameter:
iris score
Basis:
mean
Remarks:
over all male animals
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
over all female animals
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
over all animals
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
over all male animals
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
over all female animals
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
over all animals
Time point:
24/48/72 h
Score:
0.8
Max. score:
1
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
over all male animals
Time point:
24/48/72 h
Score:
0.44
Max. score:
2
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
over all female animals
Time point:
24/48/72 h
Score:
0.55
Max. score:
2
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
over all animals
Time point:
24/48/72 h
Score:
0.5
Max. score:
2
Reversibility:
fully reversible within: 8 days
Irritant / corrosive response data:
Slight (grade 1 in 5) to moderate (grade 2 in 1) redness of the conjunctiva, moderate to marked chemosis (grades 2, 3, and 4 in 1, 4 and 1 rabbit, respectively) and marked discharge (grade 3) were observed 1 hour after dosing. Five of the six animals had very slight to slight opacity at 1 hour. All occular effects were resolved by the end of the study.
Other effects:
There was no effect of test material on body weight.

None

Interpretation of results:
not irritating
Conclusions:
Based on the results, dipropylene glycol-n-propyl ether is not irritating to the eyes.
Executive summary:

Dipropylene glycol n-propyl ether (DPnP), which has a purity of 99.32% (by weight), was assessed for the potential to cause ocular irritation after instillation of a 0.1 ml aliquot into the conjunctival sac of the right eye of six New Zealand White rabbits.

 

Examination of the eyes revealed slight to moderate redness of the conjunctiva, moderate to marked chemosis, and marked discharge one hour after dosing, in all animals. Five of the six animals had very slight to slight opacity, at the one hour read.

 

The redness, chemosis, discharge and corneal opacity diminished or resolved in all animals during the following three days. All ocular effects were resolved by seven days post dosing, and the test was terminated. Instillation of dipropylene glycol n-propyl ether into the eye had no effect on body weight.

 

Based on the results, dipropylene glycol-n-propyl ether is not irritating to the eyes.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation study in rabbits:

Dipropylene glycol n-propyl ether (DpnP, purity 99.32% by weight) was evaluated for primary dermal irritaion. Aliquots of 0.5 ml of DPnP were applied for four hours to the intact skin on the back of six New Zealand White rabbits. Very slight erythema was observed on two of the six rabbits within 30 minutes of test material removal. Three of the six rabbits at 24 and 48 hours had very slight erythema. Very slight erythema was present on one of the six rabbits 72 hours after test material removal which was resolved by test day 7.

One of the rabbits patch was inadvertently caught under the tape and was held very tightly in place for the four hour exposure. As a result of this error in application technique, the rabbit had severe erythema and gradually diminishing edema for the remainder of the study, neither of which were interpreted to be compond related. The test was terminated 14 days after test material removal. Dermal application of 0.5 ml dipropylene glycol n-propyl ether had no effect on body weight. Based on the results of the study, dipropylene glycol n-propyl ether will not be classified as irritating.

Eye irritation study in rabbits:

There are two studies available for this substance. In the first study, Dipropylene glycol n-propyl ether (DPnP), purity of 99.32% (by weight), was assessed for the potential to cause ocular irritation after instillation of a 0.1 ml aliquot into the conjunctival sac of the right eye of six New Zealand White rabbits. Examination of the eyes revealed slight to moderate redness of the conjunctiva, moderate to marked chemosis, and marked discharge one hour after dosing, in all animals. Five of the six animals had very slight to slight opacity, at the one hour read.

 

The redness, chemosis, discharge and corneal opacity diminished or resolved in all animals during the following three days. All ocular effects were resolved by seven days post dosing, and the test was terminated. Instillation of dipropylene glycol n-propyl ether into the eye had no effect on body weight. Based on the results, dipropylene glycoln-propyl ether can be classified as a mild eye irritant.

In the second study, 0.1 ml of ARCOSOLV® DPnP (Dipropylene Glycol mono-n-Propyl Ether) was instilled into the lower conjunctival sac of the right eye. The eyelid was held closed for approximately 1 second and released. A washout followed, consisting of 60 mL of deionized water over a period of approximately 30-40 seconds, commencing approximately 30 seconds after dosing. The left eye of each animal was manipulated in an identical manner to simulate the dosing of the right eye and served as a contralateral control. The eyes were examined for ocular reactions in accordance with the method of Draize at approximately 1, 24, 48 and 72 hours after dosing and on study days 4, 7, 10, 14, 17 and 21, if irritation persisted. Sodium fluorescein was used to aid in revealing possible corneal damage at 24 hours and at all subsequent observations.

Conjunctival irritation (grades 1, 2, 3 and 4) were noted for all animals. Positive corneal irritation (grade 1) was noted for 1 animal 48 hours post-dosing and subsided by the 72 hour post-dosing observation. Conjunctival irritation noted at study termination (study day 21).

Based on the results, ARCOSOLV® DPnP (Dipropylene Glycol mono-n-Propyl Ether) can be classified as a mild eye irritant., however the weight of evidence indicates that the substance will not be classified for eye irritation.


Justification for selection of skin irritation / corrosion endpoint:
Only a single, well conducted study is available.

Justification for selection of eye irritation endpoint:
2 reliable studies available, however this study best characterises the irritation potential.

Justification for classification or non-classification

Skin irritation study in rabbits:

Based on the results of the study and Guidance to Regulation (EC) No. 1272/2008 on Classification, Labelling and Packaging of substances and mixtures, dipropylene glycol n-propyl ether will not be classified as irritating.

Eye irritation study in rabbits:

Based on the results of the studies and Guidance to Regulation (EC) No. 1272/2008 on Classification, Labelling and Packaging of substances and mixtures, dipropylene glycol n-propyl ether will not be classified as an eye irritant.