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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
Annex V (Maximisation test). 1992
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The skin sensitisation study was performed before adoption of the LLNA test in 2002.

Test material

Constituent 1
Chemical structure
Reference substance name:
O,O-didodecyl [({[bis(dodecyloxy)(sulfanylidene)-λ⁵-phosphanyl]sulfanyl}zincio)sulfanyl]phosphonothioate
EC Number:
948-067-3
Molecular formula:
C48H100O4P2S4Zn
IUPAC Name:
O,O-didodecyl [({[bis(dodecyloxy)(sulfanylidene)-λ⁵-phosphanyl]sulfanyl}zincio)sulfanyl]phosphonothioate
Test material form:
liquid: viscous

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: reputable commercial supplier
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 389 - 450 g
- Housing: The animals were housed singly or in pairs in solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-23°C
- Humidity (%): 51-74%
- Air changes (per hr): ca. 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12h light and 12h dark

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal
Vehicle:
other: arachis oil and Freud's Complete Adjuvant (1:1 mixture with distilled water)
Concentration / amount:
0.1% w/v in arachis oil BP and 0.1% w/v in Freud's Complete Adjuvant (1:1 mixture with distilled water)
Day(s)/duration:
7 days after intradermal induction the same sites of the animals were further induced by epicutaneous exposure with a 50% v/v concentration in arachis oil fixed for two days.
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Concentration / amount:
50% and 25%
Day(s)/duration:
1 day
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Number of animals in test group: 10
Number of animals in negative control group: 5
Details on study design:
RANGE FINDING TESTS:
For intradermal induction four concentrations (0.1, 0.5, 1 and 5%) in arachis oil were used indicating that 0.1% caused mild to moderate skin irritation.
For topical induction 10, 25, 50, and 75% in arachis oil diluted substance was used indicating that 50% diluted substance caused mild irritation.
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 exposures, first intradermal induction followed after 7 days by topical induction with 50% diluted substance for 2 days.
- Exposure period: intradermal plus 2 days topical induction of the same animals
- Test groups: 1 test group of 10 animals
- Control group: 1 control group of 5 animals
- Site: shoulder region
- Frequency of applications:
- Duration:
- Concentrations:

B. CHALLENGE EXPOSURE
- No. of exposures: 1 exposure
- Day(s) of challenge:
- Exposure period: 1 day
- Test groups:
- Control group:
- Site: flank region
- Concentrations: 50% n arachis oil to the right side, 25% in arachis oil to the left side
- Evaluation (hr after challenge): 24 h and 48 h after challange

OTHER:
Positive control substance(s):
yes
Remarks:
2-mercaptobenzothiazole

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50%
No. with + reactions:
1
Total no. in group:
4
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
4
Reading:
1st reading
Group:
positive control
Dose level:
25%
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation

Any other information on results incl. tables

see result tables attached as background material

Applicant's summary and conclusion

Interpretation of results:
other: Category 1 (skin sensitising), EU