2-ethoxy-1-methylethyl acetate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study design (OECD 406 and EU Method B.6), but with no positive control group.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

EU Method B.6 (Skin Sensitization)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

A reliable existing GPMT study is already available.

Test material

Test material information

Constituent 1

Reference substance name:

2-ethoxy-1-methylethyl acetate

EC Number:

259-370-9

EC Name:

2-ethoxy-1-methylethyl acetate

Cas Number:

54839-24-6

Molecular formula:

C7H14O3

IUPAC Name:

2-ethoxy-1-methylethyl acetate

Details on test material:

- Name of test material (as cited in study report): Ethoxypropyl acetate
- Physical state: Liquid
- Analytical purity: >98.5%
- Storage condition of test material: At ambient temperature

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Hartley / Dunkin

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Each animal was identified by ear tattoo
- Source: D. Hall, Newchurch, Staffordshire, England
- Weight at study initiation: 370 to 490 g
- Housing: Animals were housed in suspended cages with wire mesh floors.
- Diet: Ad libitum access to Vitamin C-enriched Guinea-Pig Diet F.D.1 (Special Diets Services Limited). Hay was provided once weekly.
- Water: Ad libitum access to tap water.
- Acclimation period: Animals selected for study were acclimated to the laboratory environment.

ENVIRONMENTAL CONDITIONS
- Temperature: Animal room temperature was approximately 21 degrees C.
- Humidity: Animal room relative humidity was 30 – 70%.
- Air changes: Approximately 15 changes per hour
- Photoperiod: 12 hours of artificial light in each 24 hour period

IN-LIFE DATES: From: 13 August 1985 To: 9 September, 1985

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

other: Liquid paraffin

Induction 2

Concentration / amount:

Induction (intradermal injection) – 7.5% v/v in liquid paraffin, and 7.5% in a 50:50 mixture of Freund’s complete adjuvant and liquid paraffin
Induction (topical) – undiluted
Challenge (topical) – 50% and 20% v/v in liquid paraffin

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

other: Liquid paraffin

Challenge 2

Concentration / amount:

Induction (intradermal injection) – 7.5% v/v in liquid paraffin, and 7.5% in a 50:50 mixture of Freund’s complete adjuvant and liquid paraffin
Induction (topical) – undiluted
Challenge (topical) – 50% and 20% v/v in liquid paraffin

No. of animals per dose:

20 (test group)
10 (controls)

Details on study design:

RANGE FINDING TESTS:
The intradermal and topical irritancy of a range of dilutions of ethoxypropyl acetate in liquid paraffin was investigated to identify a) irritant test substance concentrations suitable for the induction phase of the main study and b) non-irritant concentrations by the topical route of administration for the challenge phase.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Intradermal injections – Three pairs (left and right side of interscapular region) of injections:
1) Freund’s complete adjuvant (Difco laboratories, Detroit, MI) diluted with an equal volume of water
2) Ethoxypropyl acetate, 7.5% v/v in liquid paraffin
3) Ethoxypropyl acetate, 7.5% v/v in a 50:50 mixture of FCA and liquid paraffin

Topical application – One week after injections in the same interscapular area. A 2 x 4 cm patch of Whatman No. 3 paper was saturated with ethoxypropyl acetate as supplied. The patch was placed on the skin and covered by a length of impermeable plastic adhesive tape (5 cm width “Blenderm”). This in turn was firmly secured by elastic adhesive bandage (“Elastoplast” 5 cm width) wound round the torso of the animal and fixed with “Sleek” impervious plastic adhesive tape.
- Exposure period: Topical application was left in place for 48 hours.
- Control group: The control animals were treated similarly to the test animals with the exception that the test substance was omitted.

B. CHALLENGE EXPOSURE
- No. of exposures: A single challenge exposure
- Day(s) of challenge: 2 weeks after the induction exposures
- Exposure period: 24 hours
- Test groups: A 2 x 2 cm patch of Whatman No. 3 paper was saturated with approximately 0.2 ml of ethoxypropyl acetate, 50% v/v in liquid paraffin and applied to an anterior site on the flank. Ethoxypropyl acetate, 20% in liquid paraffin was applied in a similar manner to a posterior site. The patches were sealed to the flank for 24 hours under strips of “Blenderm” covered by “Elastoplast” wound round the trunk and secured with “Sleek”.
- Control group: Treated similarly to the test group.
- Evaluation (hr after challenge): Challenge sites were evaluated 24, 48 and 72 hours after removal of the patches. Sites were scored for erythema and eschar formation (Grade 0 – 4) and oedema (Grade 0 – 4). A test animal was considered to show positive evidence of delayed contact hypersensitivity if the observed dermal reaction at challenge was definitely more marked and / or persistent than the maximum reaction seen in animals of the control group.

Positive control substance(s):

no

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

50% in liquid paraffin

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50% in liquid paraffin. No with. + reactions: 0.0. Total no. in groups: 20.0.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50% in liquid paraffin

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50% in liquid paraffin. No with. + reactions: 0.0. Total no. in groups: 20.0.

Results 3

Reading:

other: 3rd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

50% in liquid paraffin

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 50% in liquid paraffin. No with. + reactions: 0.0. Total no. in groups: 20.0.

Any other information on results incl. tables

One control animal was found in poor condition and euthanized during the induction period. All challenges with 20% in liquid paraffin also produced no reaction in any animal at any time point.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

Based on these results, the study authors concluded that ethoxypropyl acetate did not produce any evidence of delayed contact hypersensitivity.

Executive summary:

In a guideline and GLP skin sensitization study using the guinea pig maximization protocol, ethoxypropyl acetate did not induce delayed contact hypersensitivity.