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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:
1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP, guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
adequate data is alredy existing

Test material

Constituent 1
Chemical structure
Reference substance name:
2-ethylhexyl diphenyl phosphite
EC Number:
239-716-5
EC Name:
2-ethylhexyl diphenyl phosphite
Cas Number:
15647-08-2
Molecular formula:
C20H27O3P
IUPAC Name:
phosphorous acid, 2-ethylhexyl diphenyl ester
Test material form:
other: liquid
Details on test material:
Lankromark LE98
A clear very pale yellow liquid
Received at lab: 26 May 1995

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
Animals obtained from D. Hall Newchurch, Staffordshire, England
Animals were 282 to 344 gram upon arrival and 4-5 weeks in age.
Animals were acclimiatised 5 days prior to allocation in the study.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: Alembicol D
Concentration / amount:
Injectibles were prepared as follows:
1. Freund's complete adjuvant diluted with equal parts water
2. 5% v/v test material in Alembicol D
3. 5% v/v test material in 1:1 mixture of Freund's complete adujvant and Alembicol D.

Induction topcial application was prepared as follows:
50% v/v test material in Alembicol D

Challenge doses were 30% v/v and 15% v/v in Alembicol D.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: Alembicol D
Concentration / amount:
Injectibles were prepared as follows:
1. Freund's complete adjuvant diluted with equal parts water
2. 5% v/v test material in Alembicol D
3. 5% v/v test material in 1:1 mixture of Freund's complete adujvant and Alembicol D.

Induction topcial application was prepared as follows:
50% v/v test material in Alembicol D

Challenge doses were 30% v/v and 15% v/v in Alembicol D.
No. of animals per dose:
5 control
10 test animals
Details on study design:
A 40x60 mm area of the dorsal skin on the scapular region was clipped of hair. Three pairs of intradermal injections were within the clipped area.

One week after the injections, the same are area was clipped and shaved free of hair. A 20x40 mm patch of Whatman No. 3 paper was saturated with 0.4 mL of 50% v/v test material in Alembicol D. The patch was coverd using impermeable plastic adhesive (Blenderm) and secured in place with Elastoplast. The dressing was left in place for 48 hours.
Challenge controls:
The control and test animals were challenged topically 2 weeks after the topical induction application using 2-ethylhexyl diphenyl phosphite at 30% and 15% v/v in Alembicol D.

Hair was removed on the left flank of each animal and two separate 20x20 mm patches, one on the posterior and one on the anterior, were covered with Whatman No. 3 paper which was saturated with 0.2 ml of either 30% v/v or 15% v/v solution as described above. The patches were sealed for 24 hours under strips of Blenderm and covered by Elastoplast around the trunk and secured with Sleek.
Positive control substance(s):
yes
Remarks:
Hexyl cinnamic aldehyde

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
30% v/v
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
Positive esponses were slight to moderate.
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 30% v/v. No with. + reactions: 8.0. Total no. in groups: 10.0. Clinical observations: Positive esponses were slight to moderate..
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
15 v/v
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
Positive responses were slight
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 15 v/v. No with. + reactions: 8.0. Total no. in groups: 10.0. Clinical observations: Positive responses were slight.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
30% v/v
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
Positive responses were slight, one moderate
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 30% v/v. No with. + reactions: 8.0. Total no. in groups: 10.0. Clinical observations: Positive responses were slight, one moderate.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
15% v/v
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
Positive responses were slight
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 15% v/v. No with. + reactions: 6.0. Total no. in groups: 10.0. Clinical observations: Positive responses were slight.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
30% v/v
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
Responses were all slight
Remarks on result:
other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 30% v/v. No with. + reactions: 8.0. Total no. in groups: 10.0. Clinical observations: Responses were all slight.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
15% v/v
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
Positive responses were all slight
Remarks on result:
other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 15% v/v. No with. + reactions: 3.0. Total no. in groups: 10.0. Clinical observations: Positive responses were all slight.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The study report found positive responses in 8 of 10 animals in the 30% v/v dose group, indicating that the substance is a skin sensitiser.
Executive summary:

In a well conducted, GLP, guideline study, Lankromark LE98 (2 -ethylhexyl diphenyl phosphite) was found to be a skin sensitiser. There was a clear response in 8 of 10 animals at the 30% v/v challenge solution, though the response was weaker at the 15% v/v challenge solution. Under the current classifiction scheme these results are consistent with the substance being classified as a skin sensitiser but not a severe skin sensitiser.