Registration Dossier

Administrative data

Description of key information

GLP guideline studies for skin- and eye- irritation are available for propylene glycol methyl ether. These studies are supported by several non-GLP studies equivalent or similar to OECD guidelines 404 and 405.

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:
1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study methodology followed was equivalent or similar to EU Method B.4 and was conducted in accordance with the Principles of GLP
Qualifier:
equivalent or similar to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: in-house
- Age at study initiation: 4-9 months
- Weight at study initiation: 4529-4920 g
- Housing: individual
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-19 °C
- Humidity (%): not specified in the report
- Air changes (per hr): not specified in the report
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle
Type of coverage:
semiocclusive
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:
Observations were made at 30 minutes after patch removal and 24, 48, 72 hours and 7 days after application
Number of animals:
3 male + 3 female
Details on study design:
TEST SITE
- Area of exposure: dorsal area between the shoulders and hindquaters
- Type of wrap if used: ealstic adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: approximately 4 hours post-exposure

SCORING SYSTEM: Draize method
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0
Remarks on result:
other: male
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Remarks on result:
other: male
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0
Remarks on result:
other: male
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: 24, 48 and 72 hours
Score:
0
Remarks on result:
other: female
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: 24, 48 and 72 hours
Score:
0
Remarks on result:
other: female
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: 24, 48 and 72 hours
Score:
0
Remarks on result:
other: female
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Remarks on result:
other: males and females
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0
Remarks on result:
other: male
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Remarks on result:
other: male
Irritation parameter:
edema score
Basis:
animal #4
Time point:
other: 24, 48 and 72 hours
Score:
0
Remarks on result:
other: female
Irritation parameter:
edema score
Basis:
animal #5
Time point:
other: 24, 48 and 72 hours
Score:
0
Remarks on result:
other: female
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0
Remarks on result:
other: male
Irritation parameter:
edema score
Basis:
animal #6
Time point:
other: 24, 48 and 72 hours
Score:
0
Remarks on result:
other: female
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Remarks on result:
other: males and females
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24, 48 and 72 hour scores
Score:
0
Irritant / corrosive response data:
No skin reactions were observed from the application of undiluted methyl proxitol to rabbit skin, consequently the group mean 24, 48 and 72 hours scores for erythema and oedema were zero
Other effects:
not applicable
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of the study, methyl proxitol was concluded as not irritating to semi-occluded rabbit skin. Mean scores for erythema and edema were 0 for all animals.
Executive summary:

Skin irritation study of Methyl proxitol was evaluated in rabbits (3 males + 3 females) and no skin were observed from the application of undiluted methyl proxitol to rabbit skin, consequently the group mean 24, 48 and 72 hours scores for erythema and oedema were zero. Based on the results of the study, methyl proxitol was concluded as not irritating to semi-occluded rabbit skin.

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:
1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study methodology followed was equivalent or similar to EU Method B.5 and was conducted in accordance with the Principles of GLP
Qualifier:
equivalent or similar to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: in-house
- Age at study initiation: 4-9 months
- Weight at study initiation: 4785-4956 g
- Housing: individual
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-19 °C
- Humidity (%): not specified in the report
- Air changes (per hr): not specified in the report
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 ml of undiluted methyl proxitol
Duration of treatment / exposure:
single exposure
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3 male + 3 female rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: 1, 24, 48, 72 hours and 7 days post-exposure

SCORING SYSTEM: Draize scoring method and Kay and Calandra

TOOL USED TO ASSESS SCORE: visual assessment of eye irritancy was made. In the event of any corneal damage, visualization was aided by the instillation of one drop of 2% fluorescein solution
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 24, 48 and 72 hours
Score:
0.1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 24, 48 and 72 hours
Score:
1.5
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 24, 48 and 72 hours
Score:
0.6
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Conjunctival redness, chemosis and discharge, corneal opacity and damage to the iris were assessed and the scores at 1 hour, 24, 48 and 72 hours and 7 days were calculated. Refer to table 1 for further details
Other effects:
The instillation of undiluted methyl proxitol into the conjunctival sac of one eye of each of the six rabbits resulted in severe initial pain
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of the study, Methyl proxitol was classifed as not irritating to rabbit eye according to EU criteria.
Executive summary:

The instillation of undiluted Methyl proxitol into the conjunctival sac of one eye of each of six rabbits resulted in severe initial pain. The conjunctival redness, chemosis and discharge, corneal opacity and damage to the iris were assessed and the scores at 1 hour, 24, 48 and 72 hours and 7 days were calculated. One rabbit showed transient corneal opacity.

On the basis of the modified Kay and Calandra grading scheme, methyl proxitol was classifed as mildly irritating to rabbit eyes. The group mean 24, 48 and 72 hour scores for redness, chemosis, corneal opacity and iritic effects were 1.5, 0.6, 0.1 and 0, respectively. On the basis of these scores, methyl proxitol was not classified as irritating.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Several skin and eye irritation studies conducted according to the OECD guidelines or equivalent methodologies are available. All studies demonstrate that propylene glycol methyl ether is not an irritant to the skin or eyes.

No data on respiratory irritation is available and given the absence of skin and eye irritation it is concluded that this substance will not have a potential for respiratory irritation.


Justification for selection of skin irritation / corrosion endpoint:
The study methodology followed was equivalent or similar to EU Method B.4 and was conducted in accordance with the Principles of GLP.

Justification for selection of eye irritation endpoint:
The study methodology followed was equivalent or similar to EU Method B.5 and was conducted in accordance with the Principles of GLP

Justification for classification or non-classification

Skin irritation: according to EEC Council Directive 67/548/EEC (amended by Directive 83/467/EEC) the mean value for erythema and edema scores was 0 for all animals at any time. According to annex VI of the directive propylene glycol methyl ether is not classified as skin irritant.

Eye irritation: according to the annex VI of the council directive 67/548 EEC (amended by directive 83/467 EEC) the average scores over all animals

cornea opacity, iris lesions, conjunctivae and chemosis were 0.1, 0, 1.5 and 0.6, respectively at 24, 48 and 72 hours. According to EEC criteria no classification for eye irritancy is required.