Registration Dossier

Administrative data

Description of key information

Ethoxypropyl acetate is mildly irritating to the rabbit eye, and is minimally irritating to semi-occluded rabbit skin.

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (EU Method B.4 and OECD 404).
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
Eu Method B.4 (Acute Toxicity: Dermal Irritation/Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Each animal was identified by a numbered aluminium tag placed through the edge of one ear.
- Source: Rosemead Rabbits, Rosemead, Essex, UK
- Age at study initiation: Approximately 10 to 11 weeks
- Sex: males
- Weight at study initiation: 2.2 to 2.5 kg
- Housing: Individually in metal cages with perforated floors
- Diet: Ad libitum access to SDS Standard Rabbit Diet
- Water: Ad libitum access to tap water
- Acclimation period: Animals were acclimated to the laboratory environment (period not stated)

ENVIRONMENTAL CONDITIONS
- Temperature: Approximately 19 degrees C
- Humidity: 30 – 70 % relative humidity
- Air changes: Approximately 19 air changes per hour
- Photoperiod: 12 hours of artificial light (0700-1900 hours) in each 24 hour period.

IN-LIFE DATES: From: 30 July, 1985 To: 2 August, 1985
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml

Duration of treatment / exposure:
4 hours.
Observation period:
Examination of the treated skin was made on Day 1 (i.e. approximately 30 minutes after removal of the patches), and on Days 2, 3 and 4.
Number of animals:
Three.
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm square
- % coverage:
- Type of wrap if used: Guaze pad occluded with ‘Elastoplast’ elastic adhesive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Distilled water
- Time after start of exposure: 4 hours after treatment

SCORING SYSTEM:
Erythema and eschar formation (Grades 0 – 4)
Oedema formation (Grades 0 – 4)
Other lesions described
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72hrs
Score:
0.44
Max. score:
4
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: Mean of 3 animals tested. Maximum score observed 1.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72hrs
Score:
0.22
Max. score:
4
Reversibility:
fully reversible within: 2 days
Remarks on result:
other: Mean of 3 animals tested. Maximum score observed 1.
Irritant / corrosive response data:
Very slight (Grade 1) erythema, with or without very slight oedema was seen in two animals on Days 2 and 3 only. These responses were completed resolved on Day 4. The remaining animal showed no observable response to treatment.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A single semi-occlusive application of ethoxypropyl acetate to intact rabbit skin for 4 hours elicited very slight dermal irritation. Based on these results, ethoxypropyl acetate is not classified as an irritant, and does not require labeling with risk phrase R38: ‘Irritating to skin’.
Executive summary:

In a guideline and GLP in vivo rabbit skin irritation study, a single semi-occlusive application of ethoxypropyl acetate for 4 hours elicited very slight dermal irritation. The response was well below the threshold for classification as a skin irritant.

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (EU Method B.5 and OECD 405).
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
EU Method B.5 (Acute toxicity Eye Irritation/Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Each animal was identified by a numbered aluminium tag placed through the edge of one ear.
- Source: Rosemead Rabbits, Rosemead, Essex, UK
- Age at study initiation: Approximately 10 to 12 weeks
- Weight at study initiation: 2.2 – 2.7 kg
- Housing: Individually in metal cages with perforated floors
- Diet: Ad libitum access to SDS Standard Rabbit Diet
- Water: Ad libitum access to tap water
- Acclimation period: Animals were acclimated to the laboratory environment (period not stated)

ENVIRONMENTAL CONDITIONS
- Temperature: Approximately 19 degrees C
- Humidity: 30 – 70 % relative humidity
- Air changes (per hr): Approximately 19 air changes per hour
- Photoperiod: 12 hours of artificial light (0700-1900 hours) in each 24 hour period.


IN-LIFE DATES: From: 5 August, 1985 To: 12 August, 1985.
Vehicle:
unchanged (no vehicle)
Controls:
other: The contralateral eye of each animal remained untreated and served as a control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml was placed into the everted lid of one eye of each animal.
Observation period (in vivo):
Examination of the eyes was made after 1 hour and 1, 2, 3, 4, and 7 days after instillation.
Number of animals or in vitro replicates:
Two males and one female
Details on study design:
SCORING SYSTEM:
Cornea (Grade 0 – 4)
Iris (Grade 0 – 2)
Conjunctiva Redness (Grade 0 – 3)
Conjunctiva Chemosis (Grade 0 – 4)
Other lesions described

TOOL USED TO ASSESS SCORE:
Observation of the eyes was aided by the use of a handheld torch.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72hr
Score:
0.44
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, 72hr
Score:
0.11
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
No corneal damage or iridial effect was observed in any animal at any time point. Maximum scores of Grade 2 redness (a diffuse crimson red colouration) and Grade 1 chemosis were observed in the conjuctiva of all three animals 1 hour following treatment. These changes were resolved in all animals by Day 3 following treatment.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Grade 2 conjuctival redness was classified as a positive response in this study. On the basis of this finding all three animals were considered to have produced a positive response to ethoxypropyl acetate. The overall mean irritation scores at 24, 48 and 72 hours were not sufficient to require labeling under Annex VI of EEC directive 67/548/EEC with the risk phrase R36: ‘Irritating to Eyes’.
Executive summary:

In an guideline and GLP in vivo rabbit eye irritation study (without washing at 24hrs), administration of 0.1 ml of ethyoxypropyl acetate produced maximum scores of Grade 2 redness and Grade 1 chemosis one hour following treatment.  These changes were resolved in all animals by Day 3.  No corneal damage or iridial inflammation was observed. The level of transient irritation produced was insufficient to meet the requirement for classification as an eye irritant.

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

Additional information

Justification for classification or non-classification

The level of response produced did not meet the requirement for classification as a skin or eye irritant. There is no data available that would suggest that ethoxypropyl acetate meets the requirement for classification as a respiratory irritant.