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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:
1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study with original study report available.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An adequate and reliable GPMT is available.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Purity 99.93%
- Lot/batch No.:shoretank 102
- Stability under test conditions: stable
- Storage condition of test material: 20C in darkness
- Other: Certificate of analysis no AA-311234.10.A01 BIS

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright-White
Sex:
female
Details on test animals and environmental conditions:
no data
TEST ANIMALS
- Source: Harlan Winkelmann, Borchen, Germany
-Strain: HsdPoc:DH
- Weight at study initiation: mean=378g, min 350, max 406g
- Housing: in groups of 5, in Macrolon cages (type 4) on soft wood granulate.
- Diet (ad libitum): ssniff Ms-H (V2233)
- Water (ad libitum): tap water from plastic bottles
- Acclimation period: 7 days min

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/-3
- Humidity (%): 50 +/-20
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: physiological saline for induction and undiluted for challenge
Concentration / amount:
For intradermal injections: Test substance diluted with isotonic saline then mixed with equal volume of FCA in 50% isotonic saline.
For dermal treatment: Test substance undiluted
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: physiological saline for induction and undiluted for challenge
Concentration / amount:
For intradermal injections: Test substance diluted with isotonic saline then mixed with equal volume of FCA in 50% isotonic saline.
For dermal treatment: Test substance undiluted
No. of animals per dose:
Treated group: 10 animals, control group 5 animals
Details on study design:
RANGE FINDING TESTS: The initial dermal tolerance of the test substance was assessed by application of test substance (0.5ml of 1, 5, 25, 100% in isotonic saline using 6 animals) to the clipped flank and left under occlusive conditions for 24 hours before evaluation. The intradermal tolerance of the test substance was assessed by two injections of test substance (2x0.1ml of 0.2, 1, 5% in isotonic saline using 3 animals) to the dorsal shoulder area and examined daily for 4 days.

MAIN STUDY
A. INTRADERMAL INDUCTION EXPOSURE (Days 0-7)
- Initial preparation: skin shaved and animals weighed. Start of study designated day 0
- No. of exposures: 1 on day 1
- Exposure period: 7 days
- Test groups: 2 intradermal injections each of 0.1ml of 5% test substance in FCA, 0.1ml of FCA and 0.1ml of 5% test substance in isotonic saline. The injection sites were left uncovered.
- Control group: Yes. Same 6 injections but with substance omitted
- Site: dorsal shoulder area

B. DERMAL INDUCTION EXPOSURE (Day 8-10)
- No. of exposures: 1 on day 8
- Exposure period: 48 hours
- Control group: Yes, same treatment but with isotonic saline.
- Site: dorsal shoulder area
- Frequency of applications: single application of 0.5ml of undiluted test substance covered by a 2x4cm patch, in turn covered by an occlusive bandage with an impermeable film and the whole covered with an elasticated bandage. After 48 hours, wrappings removed and irritant effects recorded.
- Concentrations: neat

C. CHALLENGE EXPOSURE (Days 11-24)
- No. of exposures: 1
- Day(s) of challenge: 22
- Exposure period: 24 hours occlusive
- Test groups: single application of 0.5ml of undiluted test substance covered by a 5x5cm patch, in turn covered by an occlusive bandage with an impermeable film and the whole covered with an elasticated bandage. After 24 hours, wrappings removed and effects recorded.
- Control group: Yes, using isotonic saline
- Site: shaved flank
- Concentrations: neat
- Evaluation (hr after challenge): 24 and 48 hour. Body weights recorded at 48 hrs
Challenge controls:
Yes, isotonic saline.
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100% substance
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none reported
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100% substance. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none reported.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100% substance
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none reported
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100% substance. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none reported.

Any other information on results incl. tables

No irritation response observed in range finding tests therefore the maximum concentrations were used for the main study. There was no effect on body weight. Due to strong irritation reactions of the skin after intradermal injection with FCA (both with and without test substance), 10% sodium dodecylsuphate was not applied at day 6. After removal of the patches on day 10, severe erythema dand oedema, indurated, scabbed and encrusted skin as well as necrosis was observed at the sites previously treated with FCA. Application sites treated with test substance or isotonic saline alone showed no signs of irritation.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Executive summary:

In a guinea pig maximisation study conducted to current guidelines, 2 -(2 -methoxyethoxy)ethanol showed no signs of a causing a sensitisation response. Intradermal induction was performed using 5% substance in isotonic saline and dermal induction and challenge exposures used undiluted material. There was no evidence of any irritant response either during the range finder studies.