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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
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 methodlogy followed was equivalent or similar to OECD TG 406 and the report contains sufficient information to permit a meaningful evaluation of study results
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report date:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
not applicable
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
This substance has been demonstrated to be a non-sensitizer in two guideline compliant studies, therefore potency data as generated in an LLNA is not needed.

Test material

Constituent 1
Chemical structure
Reference substance name:
2-methoxy-1-methylethyl acetate
EC Number:
203-603-9
EC Name:
2-methoxy-1-methylethyl acetate
Cas Number:
108-65-6
Molecular formula:
C6H12O3
IUPAC Name:
2-methoxy-1-methylethyl acetate
Details on test material:
- Name of test material (as cited in study report): Methyl Proxitol Acetate
- Substance type: solvent
- Physical state: colourless clear liquid
- Analytical purity: Comparisons of the infra-red spectra revealed no changes
- Impurities (identity and concentrations): Alcohol: 0.016% m/m, water: 200 ppm, HAC: 180 ppm, Unknowns: < 0.1% m/m, Peroxides: 1-12 ppm
- Composition of test material, percentage of components: MPA-1: 1.27% m/m, MPA-2: 98.6% m/m
- Lot/batch No.: U5126
- Expiration date of the lot/batch: not specified
- Stability under test conditions: stable
- Storage condition of test material: stored in the dark at room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Porcellus Ltd.
- Age at receipt: not specified
- Weight at study initiation: males: 595 - 649 grams, females: 517 - 589 grams
- Housing: group housed
- Diet (e.g. ad libitum): ad libitum (SG1 with vitamin C supplement)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23 °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

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
unchanged (no vehicle)
Concentration / amount:
induction phase - 0.1 ml of Methyl proxitol Acetate in corn oil and 0.1 ml of the test material in 50:50 FCA/corn oil
challenge phase - 0.1 ml undiluted
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
induction phase - 0.1 ml of Methyl proxitol Acetate in corn oil and 0.1 ml of the test material in 50:50 FCA/corn oil
challenge phase - 0.1 ml undiluted
No. of animals per dose:
Control - 5 male + 5 female
Test - 10 male + 10 female
Details on study design:
RANGE FINDING TESTS: 2 male and 2 female guinea pigs were closely shorn in the shoulder region using electric clippers followed by an electric razor and 0.1 ml of several dilutions (0.05, 0.1, 0.5 and 1.0 %, m/v in corn oil) of the test material injected intradermally each side of the midline. The animals were examined over the next few days to determine the maximum concentration which did not cause toxicity. Three further groups of 2 males and 2 females were taken. The flanks of each animal were closely shorn and 0.3 ml of the undiluted test material and of 75% and 50% (m/v) dilutions in corn oil applied to 4 cm x 4 cm Whatman Number 3 filter paper patches. The patches were placed on the flanks and held in place with a Sleek adhesive tape patch, then covered with an 8 cm Poroplast elastic adhesive bandage for 24 hours, after this time they were removed and the animals examined for signs of irritation.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 injections (0.1 ml) of test material in corn oil and 2 injections (0.1 ml) of test material in 50:50 FCA/corn oil. One week after intradermal injections, the same area of skin was shaved using electric clippers. A 4 cm x 4 cm patch of Whatman No.3 filter paper was moistened with 0.3 ml of the undiluted test material, placed over the site of injection and covered with a Sleek dressing. The dressing was then securely covered with an 8 cm Poroplast elastic adhesive bandage for 48 hours. Similar patches of filter paper (but moistened with corn oil only) were applied to the controls
- Exposure period: as described above
- Test groups: 1
- Control group: 1
- Site: The animals were closely shorn in the shoulder region using electric clippers followed by an electric razor, two rows of three injections were made, one of each side of the midline
- Frequency of applications: as described above
- Duration: as described above
- Concentrations: as described above

B. CHALLENGE EXPOSURE
- No. of exposures: single
- Day(s) of challenge: 2 weeks after the topical induction
- Exposure period: 24 hours
- Test groups: 1
- Control group: 1
- Site: Hair was removed from a 3 cm x 3 cm area of one flank by clipping then shaving. A 2 cm x 2 cm of Whatman No.3 filter paper, moistened with 0.1 ml of the test material, was placed over the shaved area and covered with a 3 cm square of adhesive tape, held in place by an 8 cm elastic adhesive bandage. Controls were also treated with the diluted test material.
- Concentrations: as described above
- Evaluation (hr after challenge): After 24 hours the patch was removed and the site examined for a response immediately, 24 and 48 hours after patch removal

C. OTHER
- Corn oil was 'MAZOLA' brand supplied by CPC Ltd.
- Freund's Complete Adjuvant was supplied by Difco Laboratories Ltd.
- The stability of formulations of Methyl Proxitol Acetate in corn oil was assessed using gas chromatography (GC) and were considered stable for at least 48 hours. and the stability in Freund's complete adjuvant:corn oil (1:1 v/v) were not assayed and opined to be stable for at least 7.5 hours
Challenge controls:
not specified
Positive control substance(s):
no

Results and discussion

Positive control results:
not applicable

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
undiluted Methyl Proxitol Acetate
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: undiluted Methyl Proxitol Acetate. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
undiluted Methyl Proxitol Acetate
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: undiluted Methyl Proxitol Acetate. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
corn oil
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: corn oil. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
corn oil
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: corn oil. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
other: Positive control group not used.
Group:
positive control
Remarks on result:
not measured/tested
Remarks:
Positive control group not used.

Any other information on results incl. tables

none

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Under the conditions of the study, none of the twenty test animals showed any positive response at either 24 and 48 hours after removal of the challenge patches, therefore Methyl Proxitol Acetate was not a skin sensitizer in guinea pigs
Executive summary:

In this skin sensitization study, groups of male and female guinea pigs (test group – 10 male + 10 female, control group – 5 male + 5 female) were exposed via intradermal injection to 0.1% (m/v) in corn oil, topical induction to undiluted Methyl Proxitol Acetate and topical challenge to undiluted Methyl Proxitol Acetate. The erythema resulting from the topical challenge was scored on a 4 point scale immediately on removal of the challenge patches and 24 and 48 hours later. Under the conditions of the study, none of the twenty test animals showed any positive response at either 24 and 48 hours after removal of the challenge patches, therefore Methyl Proxitol Acetate was not a skin sensitizer in guinea pigs