Registration Dossier

Diss Factsheets

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Data from GPMT study was available and it demonstrated that the test material was a skin sensitizer. LLNA data on constituents was also provided in the dossier to provide additional information.

Test material

Constituent 1
Chemical structure
Reference substance name:
Phosphorous acid, diphenyl isodecyl ester
Molecular formula:
C22H31O3P
IUPAC Name:
Phosphorous acid, diphenyl isodecyl ester
Constituent 2
Chemical structure
Reference substance name:
Triphenyl phosphite
EC Number:
202-908-4
EC Name:
Triphenyl phosphite
Cas Number:
101-02-0
Molecular formula:
C18H15O3P
IUPAC Name:
triphenyl phosphite
Constituent 3
Chemical structure
Reference substance name:
Diisodecyl phenyl phosphite
EC Number:
247-098-3
EC Name:
Diisodecyl phenyl phosphite
Cas Number:
25550-98-5
Molecular formula:
C26H47O3P
IUPAC Name:
Reaction products of triphenyl phosphite and isodecanol (1:2)
Constituent 4
Reference substance name:
Grouped, low level constituents (1) - see description
Molecular formula:
C21H29O3P and C23H33O3P
IUPAC Name:
Grouped, low level constituents (1) - see description
Constituent 5
Reference substance name:
Grouped, low level constituents (2) - see description
Molecular formula:
N/A
IUPAC Name:
Grouped, low level constituents (2) - see description
Constituent 6
Chemical structure
Reference substance name:
Triisodecyl phosphite
EC Number:
246-998-3
EC Name:
Triisodecyl phosphite
Cas Number:
25448-25-3
Molecular formula:
C30H63O3P
IUPAC Name:
Phosphorus acid, triisodecyl ester
Constituent 7
Reference substance name:
Grouped, low level constituents (3) - see description
Molecular formula:
N/A
IUPAC Name:
Grouped, low level constituents (3) - see description
Test material form:
liquid

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Induction: 0.1 DPDP v/v (injection) and 25% v/v (dermal)
Challenge 1: 10% DPDP v/v
Challenge 2: 2% DPDP v/v
Challenge 3: 5% DPDP v/v
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Induction: 0.1 DPDP v/v (injection) and 25% v/v (dermal)
Challenge 1: 10% DPDP v/v
Challenge 2: 2% DPDP v/v
Challenge 3: 5% DPDP v/v
No. of animals per dose:
10
Details on study design:
Induction injections included both the use of Freund's adjuvant 50/50 in water and just the test material without adjuvant.
Challenge controls:
No controls
Positive control substance(s):
no

Results and discussion

Positive control results:
Dermal irritation was observed after induction at those sites injected with Freund's adjuvant and a mixture of DPDP with Freund's adjuvant. DPDP on its own did not cause irritation at the injection site

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10% v/v
No. with + reactions:
7
Total no. in group:
10
Clinical observations:
Erythema and slight oedema observed in positive responses.
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10% v/v. No with. + reactions: 7.0. Total no. in groups: 10.0. Clinical observations: Erythema and slight oedema observed in positive responses..
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10% v/v
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
Erythema scores stayed the same and oedema scores generally increased.
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10% v/v. No with. + reactions: 8.0. Total no. in groups: 10.0. Clinical observations: Erythema scores stayed the same and oedema scores generally increased..
Reading:
1st reading
Hours after challenge:
72
Group:
test chemical
Dose level:
10% v/v
No. with + reactions:
7
Total no. in group:
10
Clinical observations:
Increase in erythema and oedema response in 4 of the 7 positive animals.
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 72.0. Group: test group. Dose level: 10% v/v. No with. + reactions: 7.0. Total no. in groups: 10.0. Clinical observations: Increase in erythema and oedema response in 4 of the 7 positive animals..
Reading:
2nd reading
Hours after challenge:
24
Group:
test chemical
Dose level:
2% v/v
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
Erythema and slight oedema observed.
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 24.0. Group: test group. Dose level: 2% v/v. No with. + reactions: 6.0. Total no. in groups: 10.0. Clinical observations: Erythema and slight oedema observed..
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
2% v/v
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
Clinical responses generally lessened from 24 hours.
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 2% v/v. No with. + reactions: 6.0. Total no. in groups: 10.0. Clinical observations: Clinical responses generally lessened from 24 hours..
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
2% v/v
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
Responses continued to lessen from 24 and 48 hrs.
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 2% v/v. No with. + reactions: 6.0. Total no. in groups: 10.0. Clinical observations: Responses continued to lessen from 24 and 48 hrs..
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
5% v/v
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
General slight to moderate erythema and oedema.
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 5% v/v. No with. + reactions: 9.0. Total no. in groups: 10.0. Clinical observations: General slight to moderate erythema and oedema..
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
5% v/v
No. with + reactions:
7
Total no. in group:
10
Clinical observations:
Some severe to moderate response in several animals.
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 5% v/v. No with. + reactions: 7.0. Total no. in groups: 10.0. Clinical observations: Some severe to moderate response in several animals..
Reading:
rechallenge
Hours after challenge:
72
Group:
test chemical
Dose level:
5% v/v
No. with + reactions:
7
Total no. in group:
10
Clinical observations:
Response levels similar to those at 48 hrs.
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 72.0. Group: test group. Dose level: 5% v/v. No with. + reactions: 7.0. Total no. in groups: 10.0. Clinical observations: Response levels similar to those at 48 hrs..

Any other information on results incl. tables

The first challenge application showed a mix of responses from none to mild to moderate erythema and oedema. In an attempt to clarify whether the reactions from the first challenge were skin sensitisation or irritation, the study conducted subsequent challenges at lower concentrations. In the second challenge slight to well-defined dermal reactions occurred in 6 to 10 animals. In the third challenge well-defined to moderate in 5 animals, increasing to severe responses in several animals. Slight to moderate responses were seen in the other guinea pigs, except for one animal that showed no response.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Positive dermal reactions were seen in 6 to 9 guinea pigs during the series of challenges. The study authors noted that the responses were "not entirely typical" of reactions typically seen in a sensitisation study and might have been due to irritation. The report does not state that DPDP is definitively a skin sensitizer, but the results (in consideration of other data on phosphites) appear to be indicative of skin sensitisation.
Executive summary:

Positive dermal reactions were seen in 6 to 9 guinea pigs during the series of challenges. The study authors noted that the responses were "not entirely typical" of reactions typically seen in a sensitisation study and might have been due to irritation. The report does not state that DPDP is definitively a skin sensitizer, but the results (in consideration of other data on phosphites) appear to be indicative of skin sensitisation. The substance is being classified as a skin sensitiser.

Categories Display