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Description of key information

Several skin- and eye irritation studies are available in rabbits.  Most studies were not conducted under GLP and or/to OECD guidelines, but were conducted equivalent to OECD guidelines 404 and 405. The reports have been considered to be valid. Additional acute inhalation studies were conducted in rats and mice to evaluate species differences in respiration and effects on the olfactory epithelium.

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study methodology followed was equivalent or similar to OECD TG 404 and the report contains sufficient information to permit a meaningful evalaution of study results
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
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:
TEST ANIMALS
- Source: in-house breeding colony
- Age at study initiation: 4-9 months
- Weight at study initiation:
- 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
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12 hours light:dark cycle

IN-LIFE DATES: From: April 9, 1985 To: June 7, 1985
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml of undiluted Methyl Proxitol Acetate
Duration of treatment / exposure:
4 hours
Observation period:
24, 48 and 72 hours and 7 days
Number of animals:
3 rabbits/sex
Details on study design:
TEST SITE
- Area of exposure: minimum of 2 cm x 2 cm
- % coverage: no data
- Type of wrap if used: The patch and the surrounding skin were covered by a single layer of gauze and held in place by means of an elastic adhesive bandage

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

SCORING SYSTEM: Refer to attachment 1
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of all 6 animals (3 males + 3 females)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
no data
Remarks on result:
other: no signs of irritation noted
Irritation parameter:
edema score
Basis:
mean
Remarks:
of all 6 animals (3 males + 3 females)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
no data
Remarks on result:
other: no signs of irritation noted
Irritant / corrosive response data:
There were no skin reactions following the application of undiluted Methyl Proxitol Acetate, consequently the group mean 24, 48 and 72 hour erythema and oedema scores were both zero
Other effects:
not applicable

none

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, Methyl Proxitol Acetate was classified as not irritating
Executive summary:

In this skin irritation study in rabbits, groups of 3 male and 3 femalewhite rabbits (4-9 months) were dosed with 0.5 ml of undiluted Methyl Proxitol Acetate. The dorsal hair between the shoulders and hind quaters was closely shorn with fine electric clippers. A test site was selected and a 2 cm x 2 cm lint patch with 0.5 ml of the test was applied to it. The patch and the surrounding skin were covered by a single layer of gauze and held in place by means of an elastic adhesive bandage. After 4 hours the wrapping and patch were removed. The site was examined for erythema and edema and observations were made 30 minutes after patch removal, 24, 48 and 72 hours and 7 days after application. The group mean scores were calculated and compared to the scoring system (refer to attachments). There were no skin reactions following the application of undiluted Methyl Proxitol Acetate, consequently the group mean 24, 48 and 72 hour erythema and edema scores were both zero. Under the conditions of the study, Methyl Proxitol Acetate was classified as not 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:
1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study methodology followed was equivalent or similar to OECD TG 405 and the report contained sufficient information to permit a meaningful evaluation of study results
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
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:
TEST ANIMALS
- Source: in-house breeding colony
- Age at study initiation: 4-9 months
- Weight at study initiation:
- 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
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12 hours light:dark cycle

IN-LIFE DATES: From: April 9, 1985 To: June 7, 1985
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 ml of undiluted Methyl Proxitol Acetate
Duration of treatment / exposure:
single
Observation period (in vivo):
1 hour, 24, 48 and 72 hours and 7 days
Number of animals or in vitro replicates:
3 rabbits/sex
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: immediate after instillation

SCORING SYSTEM: Draize method

TOOL USED TO ASSESS SCORE: In the event of any corneal damage visualization was aided by the instillation of 1 drop of 2% fluorescein solution
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of all 6 animals (3 male + 3 female)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: no changes observed
Irritation parameter:
iris score
Basis:
mean
Remarks:
of all 6 animals (3 male + 3 female)
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
not specified
Remarks on result:
other: no changes observed
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of all 6 animals (3 male + 3 female)
Time point:
24/48/72 h
Score:
1.2
Max. score:
3
Reversibility:
fully reversible
Remarks:
7 days, except in 1 animal
Remarks on result:
other: none
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of all 6 animals (3 male + 3 female)
Time point:
24/48/72 h
Score:
0.2
Max. score:
4
Reversibility:
fully reversible
Remarks:
7 days
Remarks on result:
other: none
Irritant / corrosive response data:
The instillation of undiluted Methyl Proxitol Acetate into the conjunctival sac of one eye of each of the six rabbits resulted in severe initial pain. The group mean 24, 48 and 72 hour scores were 1.1 for redness, 0.2 for chemosis and 0 for corneal opacity and iritic effects
Other effects:
not applicable

none

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, Methyl Proxitol Acetate is not classified as an irritant
Executive summary:

In this eye irritation study in rabbits, groups of 3 male and 3 female New Zealand white rabbits (4-9 months) were instilled with 0.1 ml of undiluted Methyl Proxitol Acetate (one eye only) into the lower conjunctival sac and the lids held together for a few seconds to prevent loss of material. The eyes were not washed. A visual assessment of eye irritancy was made at 1 hour, 24, 48 and 72 hours and 7 days after instillation, following the method of Draize and the scores so obtained were assessed as per the EU/EEC criteria and the Kay and Calandra technique. The instillation of undiluted Methyl Proxitol Acetate into the conjunctival sac of one eye of each of the six rabbits resulted in severe initial pain. The group mean 24, 48 and 72 hour scores were 1.1 for redness, 0.2 for chemosis and 0 for corneal opacity and iritic effects. Under the conditions of the study, Methyl Proxitol Acetate is not classified as an irritant

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

Respiratory irritation

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

Additional information

The studies selected as key studies are considered to be valid as they are reliable, either without restrictions (Klimisch rating 1) or with some restrictions (Klimisch rating 2). The results of the studies indicate that propylene glycol methyl ether acetate is not irritating to the skin and to eyes. Hydrolysis of PGMA to PGME and acetate in the respiratory tract could lead to mild signs of irritation. In inhalation exposure studies with PGME in human volunteers, no signs of respiratory tract irritation were observed below 100 ppm.

Skin irritation - The identified key study is the Shell (1985) study in New Zealand White rabbits and the mean erythema and edema scores were 0 for all animals (3 male + 3 female) across 24, 48 and 72 hours. In the second key study, Dow (1980), the mean erythema and edema scores were 0 for all animals (6 New Zealand White rabbits) across 24 and 72 hours.

Eye irritation - In the first key study - Shell (1985) study in New Zealand White rabbits, the mean corneal, iris, conjunctival and chemosis scores were 0, 0, 1.2 and 0.2 across 24, 48 and 72 hours, respectively. In the second key study - Dow (1980) study in New Zealand White rabbits, the mean corneal, iris, conjunctival and chemosis scores were 0.3, 0.1, 0.8 and 0.4 across 24, 48 and 72 hours, respectively.


Justification for selection of skin irritation / corrosion endpoint:
The study methodology followed was equivalent or similar to OECD TG 404

Justification for selection of eye irritation endpoint:
The study methodology followed was equivalent or similar to OECD TG 405

Justification for classification or non-classification

Propylene glycol methyl ether acetate is non-irritating to the skin and to eyes. It is not a respiratory tract irritant at usual levels of exposure. Therefore, no classification is needed for irritation.

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 acetate will not be classified as a skin irritant.

Eye irritation: According to EEC Council Directive 67/548/EEC (amended by Directive 83/467/EEC), the mean value for conreal, iris, conjunctival and chemosis scores were lower than the prescribed cut-off scores and according to Annex VI of the Directive, propylene glycol mether acetate will not be classified as an eye irritant.

In the EU risk assessment for PGMA it was concluded that although it causes some respiratory irritation in animal studies, PGMA is not expected to be severely irritant for the respiratory tract at usual PGMA levels of exposure. No classification is needed for irritation.