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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:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Although this study was not conducted in accordance with GLP, in accordance with REACH Annex XI, Section 1.1.2, the study was conducted under same scientific principles as OECD 406 Skin Sensitisation and adequate documentation of the study is provided. The study is therefore considered adequate for fulfilling this endpoint and for risk assessment purposes.

Data source

Reference
Reference Type:
publication
Title:
Sensitizing capacity and cross-reactivity of phenylglycidyl ether studies in the guinea-pig maximization test
Author:
Anne Ponten
Year:
2009
Bibliographic source:
Ponten, A., Zimerson, E. and Bruze, M. (2009) Sensitizing capacity and cross-reactivity of phenylglycidyl ether studied in the guinea-pig maximization test. Contact Dermatitis, 60: 79-84.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
not applicable
GLP compliance:
no
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
2,3-epoxypropyl phenyl ether
EC Number:
204-557-2
EC Name:
2,3-epoxypropyl phenyl ether
Cas Number:
122-60-1
Molecular formula:
C9H10O2
IUPAC Name:
2-(phenoxymethyl)oxirane
Details on test material:
Phenylglycidyl ether was purchased from Acros Organics, Geel, Belgium. The manufacturers specifications indicated a purity of 99 % which was confirmed by high-performance liquid chromatography.

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
Female albino guinea-pigs weighing 400 (+/- 20) g of the Dunkin-Hartley (M & B A/S, Ry, Denmark) were used.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
propylene glycol
Concentration / amount:
Intradermal induction: 0.55 % (w/v) (0.037 mol/l)
Topical induction: 0.83 % (w/v) (0.055 mol/l)
Challenge I: 1.7 % (w/v) (0.11 mol/l)
Challenge II: 1.7 % (w/v) (0.11 mol/l)*
* - The animals induced with PGE were additionally challenged (left flank) with a lower concentration of PGE (0.83 % (w/v) (0.055 mol/l))
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
propylene glycol
Concentration / amount:
Intradermal induction: 0.55 % (w/v) (0.037 mol/l)
Topical induction: 0.83 % (w/v) (0.055 mol/l)
Challenge I: 1.7 % (w/v) (0.11 mol/l)
Challenge II: 1.7 % (w/v) (0.11 mol/l)*
* - The animals induced with PGE were additionally challenged (left flank) with a lower concentration of PGE (0.83 % (w/v) (0.055 mol/l))
No. of animals per dose:
24 animals per test group were used in this study in addition to 12 control animals.
Details on study design:
Topical irritancy was determined by applying different concentrations of each substanceused for induction as a closed patch test for 2 days on both the neck and the flankof 4-6 animals. One week before testing, the animals were pre-treated with Freund's complete adjuvant (FCA) (Pierce, Rockford, IL, USA). Concentrations that did not cause irritation were chosen for topical induction and elicitation.

Induction Procedure
Day 0: three intradermal injections in a row at each side of the shoulder were given,
(i) 0.1 ml of FCA in water 40 % (w/v) (FCA/water 50:50 v/v);
(ii) 0.1 ml PGE dissolved in propylene glycol (0.55 % w/v);
(iii) 0.1 ml of a mixture of 40 % (w/v) FCA in propylene glycol including 0.55 % (w/v) PGE.
Day 6: pretreatment of a 2 x 4 cm area for topical induction with 0.2 ml sodium lauryl sulphate 10 % (w/v) in dimethylacetamide/acetone/ethanol 99.5 4:3:3 (v/v/v).
Day 7: topical induction with 0.2 ml of the induction substance in acetone on 2 x 4 cm piece of filter paper (130 g/m3; Munktell Filter AB, Grycksbo, Sweden) placed on Durapore (3M Health Care, St. Paul, MN, USA). The patches were covered with impermeable plastic adhesive tape (Acrylastic, Beiersdorf AG, Germany) and held in place with adhesice bandage (Durapore). The patches were left on for 2 days.
Controls: Twelve controls animals were given exactly the same treatment as described for the test animals, but with PGE excluded. In addition, six controls were given the known sensitiser 2-MP. These animals were used as a positive control.

Challenge I
Day 21: Sensitisation rate (right flank two patches), 12/24 test animals were challenged with the induction substance on both the cranial and caudal patch. 6 + 6 test animals were challenged with the induction substance on either the cranial patch or the caudal patch with vehicle alone on the other. A1-test (Imeco AB, Sodertalje, Sweden) on Durapore was used for patch testing. Thirty microlitres of the substance used for induction was applied. Acrylastic and an outer layer of Durapore held the challenge tests in place. The patches were removed after 1 day. Six of 12 control animals were tested with the induction substance on both patches, and 3 + 3 animals were patch tested with the induction substance on either the cranial or caudal patch, with vehicle alone on the other patch.

Challenge II
Animals were further challenged with induction substance as described above in addition to a challenge with a lower concentration of PGE (0.83 % (w/v)) on the left flank.

Evaluation
Day 23: the minimum criterion for a positive reaction is a confluent erythema. All tests were evaluated 1 day after the patches had been removed, i.e. 2 days after the application. First the right flanks (challenge I) were read and thereafter, the left flanks (challenge II) were read.
Positive control substance(s):
yes

Study design: in vivo (LLNA)

Positive control substance(s):
other: 2-methylol phenol
Statistics:
The number of positive animals within the test group was compared with the number of of positive animals in the control group. The number of positive test animals was also compared with the number of positive animals tested with vehicle only. Among the animals challenged with the induction substance on both cranial and caudal patches (12 test animals and 6 control animals), only one of the patches chose in advance was included.
Statistical significance was calculated with one-sided Fisher's exact test. When a significant value (P < 0.05) was obtained both in comparison with the controls tested with allergen and the animals tested with vehicle alone, the compound (i.e. PGE) was judged as a sensitiser.

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
12
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 12.0.
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
1.7 % (w/v)
No. with + reactions:
23
Total no. in group:
24
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1.7 % (w/v). No with. + reactions: 23.0. Total no. in groups: 24.0.
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.83 % (w/v)
No. with + reactions:
24
Total no. in group:
24
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.83 % (w/v). No with. + reactions: 24.0. Total no. in groups: 24.0.

Any other information on results incl. tables

PGE was found to be a strong sensitiser in the guinea-pig with 23/24 animals sensitised. No control animals had reactions to PGE (P < 0.001). Lowering the concentration for the challenge (left flank) did not reuduce the number of reacting animals. All 24 animals induced with PGE reacted when challenged with the lower concentration (left flank, P< 0.001).

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
Ph8enylglycidyl ether is a sensitiser in the guinea-pig maximisation test.

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