Registration Dossier

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:
4 October 1988 - 11 November 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was conducted according to OECD guideline 406 and under GLP conditions.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Principles of method if other than guideline:
Not relevant
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study performed prior to existance of OECD 429 test guidleine.

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of 3-[(diphenoxyphosphoryl)oxy]phenyl triphenyl 1,3-phenylene bis(phosphate) and tetraphenyl 1,3-phenylene bis(phosphate)
EC Number:
701-337-2
Cas Number:
not available
Molecular formula:
C30H24O8P2
IUPAC Name:
Reaction mass of 3-[(diphenoxyphosphoryl)oxy]phenyl triphenyl 1,3-phenylene bis(phosphate) and tetraphenyl 1,3-phenylene bis(phosphate)
Details on test material:
- Name of test material (as cited in study report): CR 733-S
- Physical state: Liquid
- Lot/batch No.: Confidential information
- Storage condition of test material: At room temperature in the dark

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga, Sulzfeld, FRG
- Age at study initiation: approx. 2 months
- Weight at study initiation: 361-510 g
- Housing: According to guideline
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum, tap water
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21
- Humidity (%): 45-75
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
propylene glycol
Concentration / amount:
Intradermal induction: 2.5%
Epicutaneous induction: 100%
1st Challenge: 10%, 25% and 100%
2nd Challenge: 100%
Challengeopen allclose all
Route:
other: epicutaneous
Vehicle:
propylene glycol
Concentration / amount:
Intradermal induction: 2.5%
Epicutaneous induction: 100%
1st Challenge: 10%, 25% and 100%
2nd Challenge: 100%
No. of animals per dose:
10 controls, 20 treated, 5 PIT
Details on study design:
RANGE FINDING TESTS:
Non-irritating intradermal injection: 2.5% test article in propylene glycol (non-irritating concentration was chosen, as 5% caused severe necrosis)
Non-irritating epicutaneous application: 100% test article (undiluted)

MAIN STUDY
A. INDUCTION EXPOSURE
According to guideline, but including SDS treatment on day 6.

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: Day 21 and 28
- Exposure period: 24 hours
- Site:
1. Left flank
2. Right flank
- Concentrations:
1. 100%, 25%, 10% and 0% (w/w)
2. 100%
- Evaluation (hr after challenge): 24 and 48 hours

OTHER
Scoring system according to Kligman, interpretation of results according to classification of Kligman (sensitisation rate)
Challenge controls:
Not relevant
Positive control substance(s):
yes
Remarks:
formaldehyde solution (37%) (seperate test)

Results and discussion

Positive control results:
A sensitization rate of 90% was obtained at a challenge concentration of 0.5% formaldehyde in Milli-RO water (after 2 times induction with 1% solution).

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Key result
Reading:
other: rechallenge (duplo)
Hours after challenge:
24
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: other: rechallenge (duplo). . Hours after challenge: 24.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
vehicle
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: vehicle. No with. + reactions: 1.0. Total no. in groups: 20.0.
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
other: rechallenge (duplo)
Hours after challenge:
24
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: rechallenge (duplo). . Hours after challenge: 24.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
100%
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 100%. No with. + reactions: 1.0. Total no. in groups: 20.0.
Key result
Reading:
other: rechallenge (duplo)
Hours after challenge:
48
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: other: rechallenge (duplo). . Hours after challenge: 48.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 20.0.
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
other: rechallenge (duplo)
Hours after challenge:
48
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: rechallenge (duplo). . Hours after challenge: 48.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
other: Formaldhyde solution 37%
Group:
positive control
Dose level:
0.5%
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation

Any other information on results incl. tables

No positive skin reactions were noted after the induction phase in both the test article and control groups.

After first challenge, a significant amount of animals were find to have positive skin reactions at the 25% and 10% concentration, but not with the undiluted test article:

Hours after reading
Concentration tested 24 hours 48 hours
100% 0/20 0/20
25% 6/20 7/20
10% 2/20 2/20
0% 0/20 1/20

Therefore, a second challenge with the undiluted test article (100%) was done (in duplo), which gave no positive reactions in the treatment group and controls.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Under the conditions of this study, the second challenge indicates that the substance CR 733-S does not possess sensitising properties. Therefore, it does not need to be classified according to Annex I of 1272/2008/EC (sensitisation rate <30%).
Executive summary:

This GPMT was performed to determine the sensitising potential of CR 733-S. Study was conducted according to OECD guideline 406 and under GLP conditions. 30 female Dunkin-Hartley guinea pigs were used. Intradermal induction was done with a 2.5% test substance solution (in propylene glycol), undiluted test article was used for epicutaneous induction. First challenge was done with undiluted test article and 25% and 10% solution, second challenge with 100% test article only (in duplo).

No positive skin reactions were noted after the induction phase in both the test article and control groups. After first challenge, a significant amount of animals were find to have positive skin reactions at the 25% and 10% concentration, but not with the undiluted test article. Therefore, a second challenge with the undiluted test article (100%) was done (in duplo). No clear positive reactions were noted in the test article or control group after the second challenge.

Under the conditions of this study, the second challenge indicates that the substance CR 733-S does not possess sensitising properties. Therefore, it does not need to be classified according to Annex I of 1272/2008/EC (sensitisation rate <30%).