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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
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
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 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.
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
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
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
Positive control results:
not applicable
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.

none

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

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In three sensitisation tests, propylene glycol methyl ether acetate did not induce sensitisation in guinea pigs. 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).

In the first key study - Shell (1985) study (according to Magnusson & Kligman), none of the guinea pigs exposed exhibited any positive reactions and similar results were also noted in the second ket study - Dow (1985).


Migrated from Short description of key information:
Three skin sensitisation studies in guinea pigs are available. Two GLP studies according Magnusson-Kligman, another one (non-GLP) according to themodified Maquire protocol. A published study (according to Magnusson & Kligman) is available as well.

Justification for selection of skin sensitisation endpoint:
The study was conducted according to OECD TG 406

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

Based on the absence of skin sensitization potential, genotoxicity and irritancy, propylene glycol methyl ether acetate is not expected to be a respiratory tract sensitizer.


Migrated from Short description of key information:
No studies on respiratory sensitization are available for propylene glycol methyl ether acetate but an assessment of sensitising potential is made using the skin skin sensitization and genotoxicity data.

Justification for classification or non-classification

In three sensitisation tests, propylene glycol methyl ether acetate did not induce sensitisation in guinea pigs. Therefore, no classification is needed for sensitisation.

According to EU criteria for classification and labeling requirements for dangerous substances as laid down in Annex VI of the EEC Council Directive 67/548 (amended by Directive 83/467 EEC), propylene glycol methyl ether acetate will not be classified as a skin or a respiratory sensitizer.